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Chokeberries (Aronia melanocarpa) and TheirProducts as a Possible Means for the Preventionand Treatment of Noncommunicable Diseasesand Unfavorable Health Effects Due to Exposureto XenobioticsSylwia Borowska and Malgorzata M. Brzoska

Abstract: Aronia melanocarpa berries (chokeberries) constitute a very rich source of numerous substances exerting abeneficial impact on health, including mainly polyphenols (proanthocyanidins, anthocyanins, flavonoids, and phenolicacids), possessing antioxidative, anti-inflammatory, antiviral, anticancer, antiatherosclerotic, hypotensive, antiplatelet, andantidiabetic properties. Thus, the consumption of products made from chokeberries is of vital importance for healthmaintenance and protection. Nowadays, due to the growing prevalence of noncommunicable diseases and ubiquitoushuman exposure to numerous man-made and naturally occurring toxic substances, some of which are dangerous even atlow amounts, it is very important to look for effective means of health protection. An important role in this regard may beplayed by A. melanocarpa berries; however, up to now the attention of scientists, nutritionists, and health practitioners hasbeen focused mainly on the effectiveness of chokeberry products in the prevention and treatment of noncommunicablediseases, while only little attention has been paid to the possibility of their use to counteract the adverse health effects ofexposure to xenobiotics. That is why in this review article the main interest has been focused on the possibility of usingchokeberries in the protection against unfavorable health effects caused by the action of substances to which humans maybe exposed environmentally and/or occupationally. The available experimental data indicate that not only the fruit butalso the leaves of A. melanocarpa and their products may be effective means for prevention and treatment of the effects oftoxic action of some xenobiotics in humans; however, further studies on this subject are necessary.

Keywords: Aronia melanocarpa berries (chokeberries), noncommunicable diseases, polyphenolic compounds, protection,xenobiotics

IntroductionIn recent years growing interest has been observed in the

possibility of using various plant products in the prevention andtreatment of noncommunicable diseases and unfavorable healtheffects of exposure to xenobiotics (Podder and others 2014; Qaderand others 2014; Hao and others 2015; Kopec and others 2016;Brzoska and others 2016a). A large body of scientific evidenceshows that a diet rich in fruits and vegetables, as well as theconsumption of some herbal products, may decrease the risk ofdeveloping various diseases (Szmitko and Verma 2005; Vidavalurand others 2006; Jin and others 2008; Lippi and others 2010;Dong and Qin 2011; Boeing and others 2012). According to the

MS 20160531 Submitted 4/4/2016, Accepted 21/6/2016. Authors Borowskaand Brzoska are with Dept. of Toxicology, Medical Univ. of Bialystok, Bialystok,Poland. Direct requires to authors Borowska or Brzoska (E-mail: [email protected] or [email protected]).

Conflict of interest: The authors declare that there are no conflicts of interest.

World Health Organization (WHO) a recommended daily intakeof fruits and vegetables should be at least 400 g (World HealthOrganization 2003). Medicinal plants are rich sources of activecompounds, including vitamins, minerals, alkaloids, saponins,essential oils, and polyphenolic compounds characterized bynumerous beneficial actions in the human body (Vidavalur andothers 2006; Whelan and others 2009; Dong and Qin 2011;Prabhakar and Doble 2011; Boeing and others 2012; Bhullar andRupasinghe 2013; Agbarya and others 2014; Muszynska and oth-ers 2015). Herbs are considered to be safe and valuable for healthso many people add them to their diet as functional food with thehope to decrease the risk of noncommunicable diseases, includingthose related to exposure to toxic substances, and to improvehealth status in the case of various illnesses (Szmitko and Verma2005; Vidavalur and others 2006; Jin and others 2008; Whelanand others 2009; Lippi and others 2010; Dong and Qin 2011;Prabhakar and Doble 2011; Boeing and others 2012; Bhullar andRupasinghe 2013; Agbarya and others 2014; de L Moreira and

982 Comprehensive Reviews in Food Science and Food Safety ! Vol. 15, 2016C⃝ 2016 Institute of Food Technologists®

doi: 10.1111/1541-4337.12221

Aronia melanocarpa in health protection . . .

others 2014; Muszynska and others 2015). Moreover, numerousplants, due to the positive impact of their ingredients on the skin,are also used in the manufacture of cosmetics (Aburjai and Nat-sheh 2003; Gediya and others 2011). Among the plant productswhich have a beneficial influence on the human organism, greentea, soy beans, pomegranates, and chokeberries are very popular.

Chokeberries (Aronia melanocarpa berries) are a very rich sourceof numerous substances exerting a favorable impact on health.However, until now the attention of researchers, nutritionists,and general health practitioners has been focused mainly on therole of aronia berries and their products in the prevention andtreatment of noncommunicable diseases, and only little attentionhas been paid to the possibility of their use in the protectionfrom the toxic action of xenobiotics. Chokeberries should notbe confused with chokecherries, which are a different fruitand belong to the Genus Prunus. The results of some studiesconducted in animal models indicate that chokeberries seem tobe a possible means to counteract the unfavorable health effectsof exposure to some xenobiotics (Niedworok and others 1995,1997; Kowalczyk and others 2003a,b; Matsumoto and others2004; Valcheva-Kuzmanova and others 2005, 2013a,b; Szaeferand others 2011; Balansky and others 2012; Roszczenko andothers 2013; Dietrich-Muszalska and others 2014; Navaneethanand Rasool 2014; Brzoska and others 2015a,b, 2016a,b; Hao andothers 2015). This issue needs special attention because humans intheir lifetime are exposed to more and more numerous chemicalsubstances dangerous to their health and some of them contributeto the development of noncommunicable diseases: heart andcirculatory diseases, cancers, diabetes, obesity and overweight,digestive system disorders, colds, some skin troubles as well asdisorders of the reproductive system and nervous system (Drazand others 2009; Hsu and others 2009; Ferraro and others 2010;Kalariya and others 2010; Shargorodsky and others 2011; Bakulskiand others 2012; Choi and others 2012; Chen and others 2013;Liu and others 2013; Moitra and others 2013; Tellez-Plaza andothers 2013; Akesson and others 2014; Sommar and others 2014;Wallin and others 2014; Wu and others 2014). Moreover, atsimultaneous, even low, exposure some of these substances mayinteract with each other leading to adverse health effects (Silinsand Hogberg 2011; Kruger and others 2012; Petti and others2013). Taking the above into account, the aim of this paper isto summarize the experimental evidence (including our ownfindings) of chokeberry effectiveness in the prevention from theaction of xenobiotics and to discuss the possible role of biologicallyactive compounds from A. melanocarpa berries in this regard. Dueto the growing problem of noncommunicable diseases and theomnipresent human exposure to numerous substances, some ofwhich are very dangerous even at low chronic exposure, it is veryimportant to look for effective ways of health protection fromthese substances. It is reasonable to assume that special interestshould be focused on the possibility of using products abundant innatural substances having a well-defined favorable impact on theorganism. Such products are the ones made from A. melanocarpaberries. That is why in this paper the main interest has beenfocused on the possibility of using chokeberries in the protectionagainst harmful health effects caused by the action of substancesto which humans may be exposed under environmental and/oroccupational conditions that include the presence of toxic heavymetals, organic solvents (including ethanol), nitrosocompounds,pesticides, and polycyclic aromatic hydrocarbons (PAH), as wellas tobacco smoke (composed of as many as about 6000 chemicalsubstances; Abdou and Elsaerei 2004; Talio and others 2010;

Figure 1–Aronia melanocarpa shrub (photo from our private collection).

Leung and others 2013; Gonzalez-Suarez and others 2014),methamphetamine, and other drugs. The wide spectrum of bene-ficial actions of the compounds present in aronia berries on humanhealth, suggesting the possibility of protective impact also underexposure to xenobiotics, the usefulness of A. melanocarpa berriesin the prevention and treatment of noncommunicable diseaseshas been summarized in this paper as well. However, the maininterest has been focused on the possibility of using aronia berriesand their products in the protection from unfavorable effects ofexposure to chemical substances and in the treatment of theseeffects. This article provides a critical overview and discussion ofthe worldwide literature and our own findings on this issue.

General Characteristic of A. melanocarpaA. melanocarpa originates from the eastern part of North

America. The plant is now cultivated almost all over the world,but it has gained the highest popularity in Europe (Skvortsovand others 1983; Niedworok and Brzozowski 2001). Aronia isa member of the Rosaceae family (Zlatanov 1999; Niedworokand Brzozowski 2001; Ochmian and others 2012). Aronia shrubs(Figure 1) can grow to the height of 2 m. In May and June theshrubs produce umbels containing about 30 small white flowerswhich ripen to purplish black berries covered by a waxy coat-ing. The harvest of chokeberries is performed during August andSeptember (Skvortsov and others 1983; Oszmianski and Wojdylo2005; Misiak and Irzyniec 2009). A. melanocarpa has no specialrequirements for cultivation. However, the use of pesticides in thecultivation of this plant should be forbidden because pesticideshave been demonstrated to decrease the content of anthocyaninsin chokeberries (Skupien and Oszmianski 2007). The quality ofaronia berries and the content of active components present inthem depend on the area of cultivation, climatic conditions dur-ing their vegetation, as well as their hydration and harvest time(Niedworok and Brzozowski 2001; Wichrowska and others 2007;Andrzejewska and others 2015).

The composition and properties of aronia berries also dependon their cultivar. In Europe, 6 cultivars of chokeberries are pop-ular “Nero,” “Galicjanka,” “Viking,” “Fertodi,” “Hugin,” and“Aron.” They differ from each other in the efficiency of juiceextraction, content of total polyphenols, anthocyanins and proan-thocyanidins, total antioxidative capacity, as well as the weight and

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diameter of the fruit (Rop and others 2010; Ochmian and oth-ers 2012; Rugina and others 2012). The “Galicjanka” cultivar ischaracterized by producing the biggest fruit (the average weight ofone fruit is 111.7 mg and their diameter ranges between 12.9 and16.4 mm), whereas the smallest berries is from “Nero” cultivar (theaverage weight of one fruit is 32.0 mg and their diameter rangesfrom 6.1 to 7.2 mm; Ochmian and others 2012). The efficiencyof juice extraction yield from various cultivars of chokeberriesdecreases in the following order: “Nero” (78.9%) > “Viking”(77.2%) > “Galicjanka” (76.8%) > “Hugin” (73.6%; Ochmianand others 2012).

Chemical Composition of A. melanocarpa BerriesThe most important ingredients of chokeberries are polyphe-

nolic compounds such as proanthocyanidins, anthocyanins,flavonoids, and phenolic acids (Figure 2 and 3; Kulling andRawel 2008; Ochmian and others 2012; Symonowicz and oth-ers 2012). Proanthocyanidins (condensed tannins) present in A.melanocarpa berries are built from (-)-epicatechin particles and theyare oligomeric and polymeric catechins responsible for the as-tringent taste of chokeberries (Niedworok and Brzozowski 2001;Oszmianski and Wojdylo 2005; Kulling and Rawel 2008). Proan-thocyanidins form complexes with proteins and polysaccharides(van Boxtel and others 2007). Anthocyanins have strong antiox-idative properties (Wu and others 2004; Jakobek and others 2007;Braunlich and others 2013c; Francik and others 2014). They arepresent in the external parts of the fruit skin and are responsiblefor the color of chokeberries (Zhao and others 2004; Symonowiczand others 2012). The content of total polyphenols and particu-lar polyphenolic compounds in chokeberries according to variousauthors is presented in Table 1.

The total content of polyphenols (including anthocyanins,proanthocyanidins, and hydroxycinnamic acids) and sugars inA. melanocarpa berries, as well as the antioxidative activity andpigmentation of chokeberry juice, depend on the date of their har-vest (Bolling and others 2015) and the kind of cultivar. “Hugin”cultivar is the richest in polyphenolic compounds. It contains23.4 mg of gallic acid equivalents per g of fresh weight (f.w.;Ochmian and others 2012). The poorest in polyphenols is “Aron”cultivar containing 15.865 ± 1.237 mg of gallic acid equivalentsper g f.w. (Rugina and others 2012). The addition of 3% β-cyclodextrin (a carbohydrate used as a stabilizer in food products)to chokeberry juice, as well as pasteurization and a decrease inthe temperature of storage and pH value of the juice, results inan increase in the level of anthocyanins in the juice (Howard andothers 2013). Moreover, the time and temperature of storage exertan influence on the content of total polyphenolic compounds andanthocyanins, as well as on the antioxidative properties of freeze-dried chokeberries (Misiak and Irzyniec 2009). The content ofpolyphenolic compounds and the antioxidative potential of thesecompounds decrease with the duration of storage, and these prop-erties are closely related to the temperature of storage. The mostappropriate is storage at 3 °C. After 6 mo of chokeberry storageat 3 °C the content of polyphenolic compounds and their antiox-idative activity decrease by 30%. A 6-mo storage of chokeberriesat 23 °C causes a decrease in the content of polyphenols by about50% and in their antioxidative activity by about 70%, while stor-age at 40 °C during the same period leads to a decrease in thecontent of polyphenolic compounds by as much as 60% (Misiakand Irzyniec 2009). The temperature of storage has a particularlygreat influence on the content of anthocyanins. The amount ofthese compounds decreases by 80% when kept at 3 °C for 6 mo

and by as much as about 90% at 23 °C or 40 °C for the same pe-riod (Misiak and Irzyniec 2009). The berries of A. melanocarpa arealso stored in the frozen form; however, there are no data on theinfluence of freezing on the stability of polyphenolic compoundspresent in chokeberries.

Apart from polyphenols, aronia berries contain other bioactiveconstituents, including vitamins, bioelements, carotenoids, tan-nins, pectins, organic acids, proteins, and bioactive carbohydrates,but they occur in smaller amounts than polyphenolic compounds.These ingredients and their quantities are listed in Table 2. Themost important among them are antioxidative vitamins (C andE), carotenoids, and minerals such as iodine, potassium, calcium,and magnesium (Table 2). The berries of aronia contain dietaryfiber as well (Borycka and Stachowiak 2008; Borycka 2012;Table 2). Also depside–ethyl 2-[(3,4-dihydroxybenzoyloxy-4,6-dihydroxyphenyl)] acetate with potent antioxidative activityis present in them (Li and others 2012). Aronia seed oilis rich in phospholipids, sterols, and tocopherol fraction(Zlatanov 1999). According to Zlatanov (1999) the content ofglyceride oil in aronia seeds is 19.3 g/kg f.w. The concentrationof all phospholipids (phosphatidylcholine, phosphatidylinositol,phosphatidylethanolamine, phosphatidic acids, lysophosphatidyl-choline, lysophosphatidylethanolamine, diphosphatidylglycerol,and monophosphatidylglycerol) is 2.8 g/kg f.w. and the to-tal amount of sterols (β-sitosterol, campesterol, stigmasterol,cholesterol, ʌ5-avenasterol, ʌ7-avenasterol, ʌ7-stigmasterol, andʌ7.25-stigmasterol) is 1.2 g/kg f.w. (Zlatanov 1999). The content oftocopherol fraction (α-tocopherol, β-tocopherol, γ -tocopherol,δ-tocopherol, and γ -tocotrienol) in chokeberry oil is 55.5 mg/kgf.w. (Zlatanov 1999).

A. melanocarpa berries should preferably originate from certi-fied ecological cultivation areas. An important property of choke-berry, which increases its usefulness in health protection, is a ratherlow accumulation of toxic metals, pesticides, nitrates(III), and ni-trates(V) (Ognik and others 2006; Klejbuk 2009; Ochmian andothers 2012). However, such data on the chemical contaminationof chokeberries are very sparse. One of the main growers of A.melanocarpa is Poland (a European country), where this shrub growsas certified cultivars, but also in many gardens without special cer-tification. The mean concentration of cadmium (Cd) in chokeber-ries originating from noncertified cultivars in the Podlasie region(recognized as ecologically pure) in Poland known for the produc-tion of fruit tea and herbal–fruit mixtures was 0.0675 ± 0.0226mg/kg d.w. and ranged between 0.0287 and 0.1386 mg/kg d.w.,while the mean concentration of lead (Pb) was 0.2329 ± 0.0823mg/kg dry weight (d.w.) and ranged from 0.1007 to 0.4364 mg/kgd.w. (Klejbuk 2009). These values did not exceed the allowed legallimits in this country (0.2 mg Cd/kg d.w. and 0.5 mg Pb/kg d.w.);however, the concentrations were higher than limits of these toxicmetals approved by the European Union and by the AustralianGovernment. According to the European regulations the limits toCd and Pb in fruits reach up to 0.05 mg/kg f.w. and 0.2 mg/kgf.w., respectively (Commission Regulation Nr 1881/2006 of De-cember 19, 2006 setting maximum levels for certain contaminantsin foodstuffs). However, in some countries, there are no any regu-lations concerning the concentrations of toxic metals in fruits. Forinstance, in Australia and New Zealand the allowed limit to Pbin fruits is 0.1 mg/kg f.w. (Australian Government Federal Reg-ister of Legislation. Australia New Zealand food standards code– Standard 1.4.1. – contaminants and natural toxicants), whilethere are no any special requirements for Cd content in fruits. InAustralia and New Zealand, there is established allowed limit for

984 Comprehensive Reviews in Food Science and Food Safety ! Vol. 15, 2016 C⃝ 2016 Institute of Food Technologists®


Proanthocyanidins Phenolic acids

• Chlorogenic acid • Neochlorogenic acid

Anthocyanins • Cyanidin 3-galactoside • Cyanidin 3-arabinoside • Cyanidin 3-glucoside • Cyanidin 3-xyloside • Pelargonidin 3-O-galactoside • Pelargonidin arabinoside

Flavonoids • Kaempherol • Quercetin • Quercetin 3-glucoside • Quercetin 3-galactoside • Quercetin 3-vicianoside • Quercetin 3-robinobioside • Quercetin 3-rutinoside

Figure 2–Polyphenolic compounds present in the berries of Aronia melanocarpa (photo from our private collection).

Quercetin Chlorogenic acid

Proanthocyanidins Anthocyanins

Figure 3–Chemical structure of polyphenolic compounds present in the berries of Aronia melanocarpa.

Cd in various food products, which ranges from 0.05 mg/kg (formeat of cattle, sheep, and pig) to 2.5 mg/kg (for kidney of cattle,sheep, and pig); whereas the limit in vegetables is 0.1 mg Cd/kg(Australian Government Federal Register of Legislation. AustraliaNew Zealand food standards code – Standard 1.4.1. – contami-nants and natural toxicants). In the United States, there is also no

established limits concerning of toxic metals in fruits and there isestablished limit only for Pb in fruit juice (FDA 2011). Accordingto FDA, the highest allowed concentration of Pb in various typesof fruit juice is equal 0.05 mg/kg (FDA 2011).

Polyphenolic compounds, including mainly chlorogenic acid,neochlorogenic acid, and caffeic acid, are also present in young



Table 1–Polyphenolic compounds and their contents in chokeberries.

Polyphenolic compound Content ReferenceTotal polyphenolic compounds 78.49 mg/g d.w. Oszmianski and Wojdylo 2005

from 10.64 ± 0.57 to 197 mg/g d.w. (as gallic acidequivalents)

Jakobek and others 2007; Rugina and others 2012;Taheri and others 2013; Hwang and others 2014

from 6.902 ± 0.088 to 25.56 mg/g f.w. Zheng and Wang 2003; Benvenuti and others 2004;Wu and others 2004; Perez-Jimenez and others 2010

Proanthocyanidins from 9.25 to 107 ± 6.6 mg/g d.w.(as catechinequivalents)

Taheri and others 2013; Hwang and others 2014

from 3.55 ± 0.49 to 6.28 ± 0.55 mg/g d.w. (asepicatechin equivalents) 1.56 to 51.82 mg/g d.w.

Rugina and others 2012

Oszmianski and Wojdylo 2005; Taheri and others 2013(-)-epicatechin 0.15 mg/g d.w. Oszmianski and Wojdylo 2005Total anthocyanins from 4.605 ± 0.029 to 14.8 mg/g f.w. Benvenuti and others 2004; Wu and others 2004

from 0.0034 to 2.7713 ± 0.251 mg/g d.w. Rugina and others 2012; Taheri and others 2013(as cyanidin 3-galactoside equivalent)

Cyanidin 3-galactoside 12.82 mg/g d.w. Oszmianski and Wojdylo 2005from 1.26 ± 0.0115 to 9.90 mg/g f.w. Zheng and Wang 2003; Wu and others 2004; Slimestad

and others 2005; Ho and others 2014Cyanidin 3-arabinoside 5.82 mg/g d.w. Oszmianski and Wojdylo 2005

from 0.83 ± 0.07 to 3.99 mg/g f.w. Zheng and Wang 2003; Wu and others 2004; Slimestadand others 2005; Ho and others 2014

Cyanidin 3-xyloside 0.527 mg/g d.w. Oszmianski and Wojdylo 2005from 0.027 ± 0.008 to 0.515 mg/g f.w. Zheng and Wang 2003; Wu and others 2004; Slimestad

and others 2005; Ho and others 2014Cyanidin 3-glucoside 0.42 mg/g d.w. Oszmianski and Wojdylo 2005

from 0.017 ± 0.025 to 0.376 mg/g f.w. Zheng and Wang 2003; Wu and others 2004; Slimestadand others 2005

Quercetin derivatives 0.7 mg/g f.w. Slimestad and others 2005Quercetin 3-rutinoside 0.15 mg/g d.w. Oszmianski and Wojdylo 2005Quercetin 3-galactoside 0.3024 ± 0.0064 mg/g f.w. Zheng and Wang 2003

0.3698 mg/g d.w. Oszmianski and Wojdylo 2005Quercetin 3-glucoside 0.2731 ± 0.0057 mg/g f.w. Zheng and Wang 2003Total flavonoids 5.3 ± 0.8 mg/g (as rutin equivalents) f.w. Hwang and others 2014

0.2164 mg/g d.w. Oszmianski and Wojdylo 2005Hydroxycinnamic acids 0.0069 to 0.0099 mg/g f.w. Taheri and others 2013Chlorogenic acid 3.018 mg/g d.w. Oszmianski and Wojdylo 2005

0.6 mg/g f.w. Slimestad and others 2005Neochlorogenic acid 2.908 mg/g d.w. Oszmianski and Wojdylo 2005

1.23 mg/g f.w. Slimestad and others 2005Caffeic acid 1.411 ± 0.014 mg/g f.w. Zheng and Wang 2003Caffeic acid derivatives 1.206 ± 0.012 mg/g f.w. Zheng and Wang 2003

leaves of A. melanocarpa (Figure 4; Skupien and others 2008; Thiand Hwang 2014), but in smaller amounts than in the berries(Table 1).

Metabolism of Polyphenolic Compounds Presentin Chokeberries

The available data on the metabolism of polyphenolic com-pounds present in chokeberries come mainly from studies con-ducted in animals and with in vitro models, but some data onthe metabolism of these compounds in the human organism arealso available. Anthocyanins, being the main polyphenol presentin chokeberries, are poorly absorbed from the small intestine andstomach (Talavera and others 2003, 2004; Kay and others 2005).In rats, the rate of absorption in the small intestine of cyanidin3-glucoside is 22.4%, while that of cyanidin 3-galactoside reaches13.6% (Talavera and others 2004). After absorption, anthocyaninsare transported with the blood to various organs and tissues,including the liver, heart, prostate, testes, brain, and body fat(Felgines and others 2009; Kirakosyan and others 2015).Kirakosyan and others (2015) have noticed that anthocyanins(derivatives of cyanidin) are distributed mainly into the urinarybladder and kidney of rats. It has been revealed that not onlyanthocyanins, but also other polyphenols (quercetin, epicatechin,and rutin) are able to cross the blood–brain barrier (Machado andothers 2008; Janle and others 2014). Polyphenolic compoundsundergo biotransformation via methylation and conjugation withglucuronic acid (Talavera and others 2004; Kay and others 2004,

2005; Lala and others 2006; Wiczkowski and others 2010). Cyani-din 3-glucoside and its methylated and glucuronidated derivativesare excreted with the bile (Talavera and others 2004) and thenwith the feces (Lala and others 2006); however, the main routeof their elimination from the body is urinary excretion (Kay andothers 2004, 2005; Wiczkowski and others 2010). The antho-cyanin metabolites are glucuronide conjugates, methylated andoxidized derivatives of cyanidin 3-galactoside, and cyanidin glu-curonide (Kay and others 2004; Wiczkowski and others 2010).The process of anthocyanin conjugation is probably responsiblefor their metabolic activation and health benefits connected withthe consumption of chokeberries and products made from them(Kay and others 2004).

Ingested hydroxycinnamic esters are first hydrolyzed in thestomach (Farrell and others 2011) and then are decomposed in thehuman colon, by the gut bacteria belonging to the Bifidobacteriumand Lactobacillus genera, to bioactive hydroxycinnamic acids(Couteau and others 2001; Raimondi and others 2015). Bifidobac-terium animalis is the only one Bifidobacterium strain occurring inthe human gut which is able to hydrolyse chlorogenic acid intocaffeic acid by the presence of the intracellular enzyme–feruloylesterase (Raimondi and others 2015). Chlorogenic acid is alreadymetabolized in the digestive system by the colonic microflorato quinic acid and caffeic acid (with antioxidative properties;Tomas-Barberan and others 2014; Gul and others in press), whichare next absorbed in the small intestine (Couteau and others 2001)and transported into the blood circulation (Stalmach and others



Table 2–Active ingredients (other than polyphenols) in chokeberries and their contents.

Ingredient Content ReferenceVitamin C 0.013 to 0.27 mg/g f.w. Tanaka and Tanaka 2001; Benvenuti and others 2004; Kulling and Rawel

2008; Andrzejewska and others 2015Vitamin E 0.008 to 0.031 mg/g f.w. Tanaka and Tanaka 2001; Sikora and others 2009Carotenoids 0.014 to 0.049 mg/g f.w. Razungles and others 1989; Sikora and others 2009β-carotene 0.0077 to 0.0167 mg/g f.w. Razungles and others 1989; Tanaka and Tanaka 2001β-cryptoxanthin 0.0046 to 0.0122 mg/g f.w. Razungles and others 1989; Tanaka and Tanaka 2001Violaxanthin 0.013 mg/g f.w. Razungles and others 1989Tannins 0.5% to 0.6% Boncheva and others 2013Dietary fiber 56 mg/g f.w. Tanaka and Tanaka 2001Pectin 0.5% to 0.6% Boncheva and others 2013Organic acids 1.1% to 1.4% Boncheva and others 2013l-mallic acid 13.1 mg/g f.w. Tanaka and Tanaka 2001Citric acid 2.1 mg/g f.w. Tanaka and Tanaka 2001Carbohydrates 10% to 18% Boncheva and others 2013Proteins 0.7% f.w. Tanaka and Tanaka 2001Sodium 0.026 mg/g f.w. Tanaka and Tanaka 2001Potassium 2.18 mg/g f.w. Tanaka and Tanaka 2001Calcium 0.322 mg/g f.w. Tanaka and Tanaka 2001Magnesium 0.162 mg/g f.w. Tanaka and Tanaka 2001Iron 0.0093 mg/g f.w. Tanaka and Tanaka 2001Zinc 0.0015 mg/g f.w. Tanaka and Tanaka 2001Folate 0.0002 mg/g f.w. Stralsjo and others 2003Vitamin B1 0.0002 mg/g f.w. Tanaka and Tanaka 2001Vitamin B2 0.0002 mg/g f.w. Tanaka and Tanaka 2001Vitamin B6 0.0003 mg/g f.w. Tanaka and Tanaka 2001Niacin 0.003 mg/g f.w. Tanaka and Tanaka 2001Pantothenic acid 0.0028 mg/g f.w. Tanaka and Tanaka 2001Vitamin K 0.0002 mg/g f.w. Tanaka and Tanaka 2001

Total polyphenols 2.279 ± 0.428 mg/g d.w.

Chlorogenic acid 0.639 ± 0.114 mg/g d.w.

Quercetin 0.288 ± 0.08 mg/g d.w.

Quercetin derivatives 0.118 ± 0.053 mg/g d.w.

p-coumaric acid 0.035 ± 0.011 mg/g d.w.

Neochlorogenic acid 0.410 ± 0.103 mg/g d.w.

Caffeic acid derivatives 0.271 ± 0.040 mg/g d.w.

Caffeic acid 0.518 ± 0.027 mg/g d.w.

Figure 4–Content of polyphenolic compounds in the leaves of Aronia melanocarpa (according to Skupien and others 2008; photo from our privatecollection).

2014). Metabolites of chlorogenic acid (dimethoxycinnamicacid, glucuronide derivatives, and sulfated caffeoylquinic acidderivatives) are excreted mainly with the urine (Zhong and others2008; Stalmach and others 2014) and also in small amounts withthe bile and feces (Zhong and others 2008).

Beneficial Health Properties and Usefulness ofChokeberries and Their Products

Chokeberries are very rarely eaten raw due to their astrin-gent taste. They are used as ingredients in products such asfruit juices, fruit spirits, wines, liqueurs, jellies, marmalades,and extracts (Table 3 and 4; Niedworok and Brzozowski 2001;Balcerek 2010; Symonowicz and others 2012; Snebergova and

others 2014). The most popular aronia extract is Aronox usedfor the production of juices and syrups, as well as dietary supple-ments in the form of pills and tablets (Niedworok and Brzozowski2001; Wolski and others 2007; Symonowicz and others 2012;Snebergova and others 2014). Extracts from A. melanocarpa berriesare also sometimes used as food colorants (Espin and others 2000;Kmiecik and others 2001; Oszmianski 2002; Wojdyło and others2008).

According to the available literature data, the total content ofpolyphenols in chokeberry extracts is higher than in the otheraronia berry products and it ranges from 192 ± 1.1 to 714.1± 7.4 mg/g d.w., while the content of anthocyanins is between5.9 and 404.5 ± 4.9 mg/g d.w. (Table 3). The concentrations



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man

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man

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hers

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Table 4–The contents of polyphenolic compounds in juices, syrup, and concentrate from chokeberries (mg/100 mL).

Polyphenolic compounds Juices Syrup Concentrate ReferenceTotal polyphenols from 665.2 to 755 ± 75 Valcheva-Kuzmanova and others 2007b, 2013b; Handeland

(as gallic acidequivalents)

and others 2014

Proanthocyanidins from 60 ± 11 to 392.62 Krajka-Kuzniak and others 2009; Valcheva-Kuzmanova andothers 2013b; Handeland and others 2014

(-)-epicatechin 1.48 Krajka-Kuzniak and others 2009Total anthocyanins 5.93 to 111.8 18.8 61.25 ± 0.06 Girones-Vilaplana and others 2012; Vlachojannis and others

2015Anthocyanins from 2.8 ± 0.1 to 45.2 ±

5.9Handeland and others 2014

(as cyanidin 3-galactosideequivalents)

106.8 ± 6.2 Valcheva-Kuzmanova and others 2007b(as cyanidin 3-glucoside

equivalents)Cyanidin 3-galactoside from 1.7 ± 0.2 to 82.21 14.41 40.84 ± 0.04 Krajka-Kuzniak and others 2009; Girones-Vilaplana and

others 2012; Valcheva-Kuzmanova and others 2013b;Handeland and others 2014; Vlachojannis and others2015

Cyanidin 3-arabinoside from 0.7 ± 0.1 to 24.99 3.63 16.51 ± 0.01 Krajka-Kuzniak and others 2009; Girones-Vilaplana andothers 2012; Valcheva-Kuzmanova and others 2013b;Handeland and others 2014; Vlachojannis and others2015

Cyanidin 3-xyloside from 0.06 to 2.1 ± 0.3 0.045 2.03 ± 0.01 Krajka-Kuzniak and others 2009; Girones-Vilaplana andothers 2012; Valcheva-Kuzmanova and others 2013b;Handeland and others 2014; Vlachojannis and others2015

Cyanidin 3-glucoside 0.24 to 5.12 0.75 1.87 Krajka-Kuzniak and others 2009; Girones-Vilaplana andothers 2012; Valcheva-Kuzmanova and others 2013b;Handeland and others 2014; Vlachojannis and others2015

Quercetin 11.8 ± 0.8 Valcheva-Kuzmanova and others 2007bQuercetin 3-rutinoside 1.68 Krajka-Kuzniak and others 2009Quercetin 3-galactoside 2.83 Krajka-Kuzniak and others 2009Quercetin 3-glucoside 2.25 Krajka-Kuzniak and others 2009Chlorogenic acid from 45.5 to 67.8 ± 2.5 Krajka-Kuzniak and others 2009; Valcheva-Kuzmanova and

others 2013b; Handeland and others 2014;Skarpanska-Stejnborn and others 2014

Neochlorogenic acid 49.21 to 84 Krajka-Kuzniak and others 2009; Valcheva-Kuzmanova andothers 2013b; Handeland and others 2014

of polyphenolic compounds in various products made fromaronia berries are presented in Table 3 and 4. Snebergova andothers (2014) have reported that the content of polyphenoliccompounds in various products made from chokeberries (juice,jam, compote, and syrup) available on the Czech market rangesfrom 2.55 to 12 mg/g (as gallic acid equivalents). Chokeberrieshave gained popularity due to their high, compared to other nat-ural products, content of polyphenolic compounds (Table 1 and5) which possess well-confirmed antioxidative, anti-inflammatory,antiviral, anticancer, antiatherosclerotic, hypotensive, antiplatelet,and antidiabetic properties as well as protective action on the bloodvessels.

Antioxidative propertiesChokeberries are characterized by strong antioxidative proper-

ties connected with the high content of polyphenolic compounds,especially anthocyanins (Jakobek and others 2007; Denev and oth-ers 2012; Braunlich and others 2013c; Francik and others 2014).Moreover, the antioxidative action of the berries is connectedwith the presence of vitamins C and E, β-carotene, and mineralssuch as zinc, copper, and selenium (Table 2; Valcheva-Kuzmanovaand others 2007a). Polyphenolic compounds act not only as di-rect free radical scavengers (Foley and others 1999; Iwahashi 2000;Lodovici and others 2001; Braunlich and others 2013c), but theyalso inhibit the activities of pro-oxidative enzymes (Braunlich andothers 2013c) and increase the activities of antioxidative enzymes(Francik and others 2014). Moreover, polyphenols play a rolein the regeneration of vitamins C and E (Dai and others 2008;

Graversen and others 2008). It has been revealed that anthocyaninsfrom chokeberry juice (mainly cyanidin 3-galactoside and cyanidin3-arabinoside) are more efficient antioxidants than polyphenoliccompounds occurring in blackcurrant and vitamin C (Graversenand others 2008). Cyanidin 3-arabinoside possesses the strongestradical-scavenging properties among the anthocyanins present inchokeberries, and it is a strong inhibitor of pro-oxidative enzymes(15-lipooxygenase and xanthine oxidase; Braunlich and others2013c). Polyphenolic compounds from A. melanocarpa berries arecharacterized by stronger radical-scavenging activity than polyphe-nols present in other berries (Jakobek and others 2007; Table 6).Anthocyanins from chokeberries are characterized by higher an-tioxidative activity against lipid oxidation induced by UV radiationin the membrane of liposomes (made from egg yolk lecithin) thananthocyanins from sloe and honeysuckle (Gabrielska and others1999). Studies performed in animal models have revealed thatpolyphenolic compounds from condensed chokeberry juice andanthocyanin dye protect from the ionizing radiation-caused gen-eration of superoxide anion by peripheral blood granulocytes.The above findings suggest that these compounds may be use-ful in the treatment of radiation sickness, whose pathomechanismis connected with the process of oxidation (Andryskowski andothers 1998a,b). Strong antioxidative properties make it possiblethat chokeberries may be effectively used in the prophylaxis andtreatment of the health disorders connected with oxidative stress,especially diabetes (Jurgonski and others 2008; Rugina and others2011, 2015; Zhu and others 2012) and cancers (Olas and others2010).



Table 5–Contents of total polyphenols in various foodstuffs.

Foodstuff Content (mg/g f.w.) ReferenceChokeberry from 6.902 ± 0.088 to 25.56 mg/g f.w. Zheng and Wang 2003; Benvenuti and others 2004;

Wu and others 2004; Perez-Jimenez and others2010

Blueberry 27.4 ± 7.4 Hwang and others 2014(as gallic acid equivalents)

Raspberry 1.256 ± 0.133 Jakobek and others 2007(as gallic acid equivalents)

Blackberry 2.488 ± 0.234 Jakobek and others 2007(as gallic acid equivalents)

Strawberry 1.005 ± 0.056 Jakobek and others 2007(as gallic acid equivalents)

Black elderberry 13.59 Perez-Jimenez and others 2010Blackcurrant 7.58 Perez-Jimenez and others 2010Plum 3.77 Perez-Jimenez and others 2010Sweet cherry 2.74 Perez-Jimenez and others 2010Black grape 1.69 Perez-Jimenez and others 2010Apple 1.36 Perez-Jimenez and others 2010Cloves 151.88 Perez-Jimenez and others 2010Cocoa powder 34.48 Perez-Jimenez and others 2010Dark chocolate 16.64 Perez-Jimenez and others 2010Flaxseed 15.28 Perez-Jimenez and others 2010Chestnut 12.15 Perez-Jimenez and others 2010Hazelnut 4.95 Perez-Jimenez and others 2010Black olive 5.69 Perez-Jimenez and others 2010Green olive 3.46 Perez-Jimenez and others 2010Curry powder 2.85 Perez-Jimenez and others 2010Coffee 2.14 Perez-Jimenez and others 2010Almond 1.87 Perez-Jimenez and others 2010Spinach 1.19 Perez-Jimenez and others 2010Black tea 1.02 Perez-Jimenez and others 2010Red wine 1.01 Perez-Jimenez and others 2010Green tea 0.89 Perez-Jimenez and others 2010Soy yogurt 0.84 Perez-Jimenez and others 2010Pure pomegranate juice 0.66 Perez-Jimenez and others 2010

The antioxdative properties of chokeberries and their productshave been confirmed among both healthy people and those suffer-ing from noncommunicable diseases (Pilaczynska-Szczesniak andothers 2005; Kardum and others 2014b; Skarpanska-Stejnbornand others 2014). Pilaczynska-Szczesniak and others (2005) havereported that the daily consumption of 150 mL of chokeberryjuice (containing 23 mg anthocyanins/100 mL) by rowers per-forming physical exercises during a 1-mo training camp decreasedthe exercise-induced oxidative damage to the red blood cells. Inanother study, it has been revealed that an 8-wk supplementa-tion with 150 mL of chokeberry juice per day by 10 members ofthe Polish Rowing Team increased the antioxidative potential ofthe plasma (Skarpanska-Stejnborn and others 2014). Kardum andothers (2014b) have reported that a 3-mo-lasting consumption of100 mL of polyphenol-rich chokeberry juice 3 times daily by 25healthy women increased the activities of antioxidative enzymessuch as superoxide dismutase (SOD) and glutathione peroxidase(GPx) in the red blood cells, and protected from lipid peroxidationin the membranes of these cells. A 12-wk-lasting consumption ofchokeberry juice by 29 healthy female volunteers decreased thelevel of thiobarbituric acid-reactive substances (TBARS) values,a marker of lipid peroxidation, and it increased the activity ofparaoxonase-1 (an enzyme responsible for antioxidative propertiesof high-density lipoproteins) in the plasma (Kardum and others2014a). The evidence of the antioxidative effectiveness of choke-berries and their products in people suffering from noncommu-nicable diseases are presented in the latter part of the paper.

Anti-inflammatory propertiesBoth chokeberry extract and juice are reported to have anti-

inflammatory properties connected with the inhibition of release

of inflammatory cytokines such as IL-6, interleukin-8 (IL-8), andtumor necrosis factor alpha (TNF-α; Appel and others 2015).Inflammatory processes contribute to the development of vari-ous pathological states, including, first of all, diabetes (Bronceland others 2010; Qin and Anderson 2012), cardiovascular disor-ders (Zapolska-Downar and others 2012; Bijak and others 2013a;Badescu and others 2015), skin diseases (Young and Young 2015),eye diseases (Ohgami and others 2005), and immune system disor-ders (Ho and others 2014; Appel and others 2015). The availableliterature data suggest that aronia berry products may protect fromthe development of these disorders by inhibiting inflammatoryprocesses (Appel and others 2015).

Appel and others (2015) have reported that chokeberry juiceimproves the immune system function by inhibiting both the re-lease of IL-6, IL-8, and TNF-α in the human peripheral mono-cytes and activating nuclear factor kappa-light-chain-enhancerof activated B cells (NF-κB) pathway in RAW264.7 mousemacrophage cells. Moreover, the authors have revealed that anaddition of selenium into the chokeberry juice increased its anti-inflammatory action in the human peripheral monocytes andRAW264.7 mouse macrophage cells by inhibiting NF-κB acti-vation, cytokine release, and prostaglandin E2 (PGE2) synthesis.

A. melanocarpa fruit extract, due to its anti-inflammatory andantioxidative properties, may also be used for the protection ofblood vessels. Zapolska-Downar and others (2012) have revealedthat chokeberry extract exerts anti-inflammatory effect in humanaortic endothelial cells by inhibiting the expression of endothelialintercellular adhesion molecule 1 and VCAM-1, as well as by de-creasing the activation of NF-κB and intracellular reactive oxygenspecies (ROS) formation in vitro. Moreover, Ohgami and others(2005) have reported, in an animal model, that chokeberry crude



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extract exerts an anti-inflammatory effect in the eyes of rats by sup-pressing the release of PGE2 and TNF-α, as well as by blockingthe expression of nitric oxide synthase (NOS) and cyclooxygenase-2, and suggested that this extract protects visual acuity probablyvia this mechanism. Unfortunately, up to now there is no evi-dence that chokeberry products may improve eyesight in humans.However, the results by Ohgami and others (2005) suggest thatchokeberries may constitute a valuable ingredient of dietary sup-plements whose role is to support visual acuity and thus furtherinvestigations on this matter are necessary.

Amin and others (2015) have reported that metabolites of cyani-din 3-glucoside (ferulic acid, protocatechuic acid, protocatechuicacid 3-glucuronide, and protocatechuic acid 4-glucuronide) atconcentrations from 0.1 to 10 µM caused a greater decrease inthe levels of inflammatory mediator proteins (interleukin 6–IL-6and vascular cell adhesion molecule 1–VCAM-1) in human vas-cular endothelial cells than the parent compound. Taking theseinto account, it can be concluded that the biotransformation ofanthocyanins increases their bioactivity.

Antibacterial propertiesChokeberries possess antibacterial activity against Escherichia coli

(Braunlich and others 2013b), Bacillus cereus (Braunlich and oth-ers 2013b; Liepina and others 2013), Staphylococcus aureus, andPseudomonas aeruginosa (Liepina and others 2013), as well as againstbacteria responsible for the development of urinary tract infections(Handeland and others 2014). According to Handeland and others(2014), an increased intake of chokeberry juice causes a strong an-tibacterial effect in people suffering from urinary tract infections.The antibacterial effect was observed after the daily consumptionof 89 mL aronia juice for 3 mo, but a more significant decreasein the incidence of urinary tract infections was observed in thegroup of people consuming 156 mL of the juice during the sameperiod of time (Handeland and others 2014). The consumptionof chokeberry juice in the amount of 89 or 156 mL daily for 3mo decreased the incidence of urinary tract infections on aver-age by 38% and 55%, respectively, among nursing home residentsin Norway (Handeland and others 2014). Taking into accountthe anti-inflammatory properties (Appel and others 2015) and an-tibacterial activity of chokeberry extract and juice (Braunlich andothers 2013b; Liepina and others 2013; Handeland and others2014) it can be supposed that aronia berry products may be usefulin the protection and treatment of immunological diseases inducedby bacteria.

Chokeberries and Their Products in the Preventionand Treatment of Noncommunicable Diseases

The growing incidence of noncommunicable diseases, includ-ing diabetes, cardiovascular diseases, depression, neurodegenerativediseases, cancer, and osteoporosis, constitutes an important publichealth problem in industrialized countries (Bhullar and Rupas-inghe 2013; Akesson and others 2014; Wolk and others 2014;Muszynska and others 2015; Siegel and others 2015). Thus, nu-merous efforts have been made to provide effective protection fromthese diseases and their treatment (Whelan and others 2009; Prab-hakar and Doble 2011; Bhullar and Rupasinghe 2013; Agbarya andothers 2014; Muszynska and others 2015). In recent years, grow-ing attention has been focused on the possibility of using naturalproducts for this purpose (Jin and others 2008; Whelan and others2009; Lippi and others 2010; Dong and Qin 2011; Prabhakar andDoble 2011; Boeing and others 2012; Bhullar and Rupasinghe2013; Agbarya and others 2014; de L Moreira and others 2014;

Muszynska and others 2015). The available literature data providestrong evidence that products made from A. melanocarpa berriesmay constitute useful strategies for the prevention and treatmentof noncommunicable diseases (Figure 5). Well-documented casesof health improvement as a result of the consumption of choke-berry products (mainly juices and extracts) in patients sufferingfrom various diseases have been reported (Simeonov and others2002; Naruszewicz and others 2003, 2007; Kowalczyk and oth-ers 2005; Broncel and others 2007, 2010; Skoczynska and others2007; Poreba and others 2009; Boncheva and others 2013; Kardumand others 2015). Moreover, there is also evidence which suggeststhe possible effectiveness of the leaves of this plant (Skupien andothers 2008). However, further epidemiological and clinical stud-ies on the usefulness of A. melanocarpa in health protection againstnoncommunicable diseases are necessary.

DiabetesDiabetes is a common public health problem in industrialized

countries (Narayan and others 2000). It has been forecast thatby 2025 the number of people with diagnosed diabetes will in-crease to at least 300 million (Narayan and others 2000). Becauseof that the prevention from the development of diabetes mellitusand elimination of risk factors leading to it are necessary. Thiscan be reached by the improvement of both a bad dietary patternand inadequate physical activity. One of the risk factors leadingto the development of type 2 diabetes (non-insulin-dependentdiabetes) is the metabolic syndrome (Broncel and others 2010).The etiology of this type of diabetes is connected with insuffi-cient insulin production and decreased sensitivity of tissues andorgans to this hormone. Oxidative stress and inflammatory pro-cesses are involved in the pathomechanisms of diabetes and thedevelopment of metabolic syndrome. This syndrome is a chronicinflammatory disorder characterized by elevated blood pressure,high level of fasting glucose in the plasma, high concentrationsof serum triglycerides, and low levels of high-density lipopro-tein (HDL) in the plasma. There is unquestionable evidence thatincluding A. melanocarpa berries and their products in the diet de-creases the risk of diabetes and increases the effectiveness of insulinby an improvement in glucose metabolism (Valcheva-Kuzmanovaand others 2007c; Jurgonski and others 2008; Qin and Anderson2012; Zhu and others 2012; Badescu and others 2015). The pos-itive impact of extracts made from chokeberries in the preventionand treatment of diabetes is a result of their antioxidative and anti-inflammtory properties (Naruszewicz and others 2007; Bronceland others 2010; Qin and Anderson 2012; Badescu and others2015; Rugina and others 2015). The effectiveness of chokeberryjuice and chokeberry extract in the protection and treatment ofdiabetes is connected with the ability of cyanidin 3-arabinosidepresent in chokeberries to inhibit the activity of α-glucosidase,an enzyme involved in the regulation of carbohydrate metabolismand the development of diabetes (Braunlich and others 2013c).Moreover, the ingredients of chokeberries exert antioxidative andanti-inflammatory action contributing to the inhibition of the de-velopment of oxidative stress and inflammatory process involvedin the pathomechanisms of diabetes and metabolic syndrome(Rugina and others 2011; Zhu and others 2012). Chlorogenicacid modulates the metabolism of glucose and lipids (Meng andothers 2013).

An extract of anthocyanins from chokeberries has been notedto exert antioxidative action in the human liver cell line (HepG2)as well as in the mouse β-pancreatic TC-3 cells treated with highdoses of glucose (Rugina and others 2011, 2015; Zhu and others



Figure 5–Confirmed and possible usefulness of the berries of Aronia melanocarpa and their products.

2012). According to Rugina and others (2015), chokeberry ex-tract increases β-pancreatic TC3 cell proliferation and pancreaticsecretion of insulin.

Moreover, it has been revealed in animal models that ingredi-ents of chokeberry juice and chokeberry extract have the abilityto indirectly increase the sensitivity to insulin (Qin and Anderson2012) and to decrease the activity of maltase in the small intestinemucosa (Jurgonski and others 2008). Qin and Anderson (2012)have reported that the extract decreased excessive weight gain andfat accumulation, as well as fasting glucose concentration and in-creased insulin concentration in the plasma of rats. The extractconsumption has also been noted to improve the plasma concen-tration of adiponectin (a hormone increasing insulin sensitivity),decrease the concentrations of TNF-α and IL-6 in the plasma, andmodulate gene expression in pathways involved in adipogenesis,inflammation, and insulin signaling (Qin and Anderson 2012).

The daily consumption of 200 mL of chokeberry juice for 3 mohas been reported to be effective in lowering the concentrationof fasting glucose in the blood (from 13.28 ± 4.55 to 9.10 ±

3.05 mmol/L) and decreasing the concentration of lipid, totalcholesterol, and glycated hemoglobin (HbA1c) in the blood in21 patients with non-insulin-dependent diabetes lasting from 6 to17 y (Simeonov and others 2002). Moreover, chokeberry extractcan be successfully used for diminishing the symptoms of metabolicsyndrome. A 2-mo consumption of 100 mg of chokeberry extract3 times daily by 25 patients with metabolic syndrome loweredtheir blood pressure, the serum concentration of endothelin-1,and the serum level of lipids and TBARS, as well as increased theactivities of antioxidative enzymes in erythrocytes (Broncel andothers 2010).

The findings by Simeonov and others (2002) allow to recognizethat the consumption of 200 mL of juice daily for at least 3 mo maybe effective in the improvement of glucose and lipid metabolismin humans. Taking the above into account, it can be concludedthat chokeberry juices and extracts are valuable products in theprevention and treatment of diabetes. Nutritionists and cliniciansrecommend the consumption of chokeberries and their productsfor diabetes prevention and support the treatment of this disease.



However, so far there is no established dose of chokeberry productsrecommended for the prevention and treatment of diabetes andmetabolic syndrome.

Cardiovascular system disordersCirculatory system disorders are the main cause of death

in industrialized countries (Lloyd-Jones and others 2010). Epi-demiological data suggest that the consumption of anthocyaninsis associated with a lower risk of cardiovascular diseases, in-cluding myocardial infarction (Szmitko and Verma 2005; Lippiand others 2010; Cassidy and others 2013). The consump-tion of aronia products (extracts and juices) has been reportedto inhibit oxidative stress and inflammatory processes in theblood vessels that contribute to the development of disordersin the cardiovascular system. It should be emphasized that pro-tective influence of chokeberries on the cardiovascular systemis a result of their antioxidative and anti-inflammatory prop-erties (Naruszewicz and others 2003, 2007; Kowalczyk andothers 2005; Bell and Gochenaur 2006; Broncel and oth-ers 2007, 2010; Olas and others 2008a; Zapolska-Downar andothers 2008; 2012; Kedzierska and others 2011; Duchnowicz andothers 2012; Bijak and others 2013a).

It has been noticed with in vivo studies in animal models, andconfirmed among human volunteers, that the consumption ofA. melanocarpa berries in various forms normalizes blood pres-sure (Naruszewicz and others 2007; Skoczynska and others 2007;Park and Park 2011; Ciocoiu and others 2013; Kardum and oth-ers 2015) and serum lipid profile (Skoczynska and others 2007;Valcheva-Kuzmanova and others 2007a,b,c,d; Poreba and others2009; Sikora and others 2012; Kim and others 2013; Kardum andothers 2015). The influence of chokeberry extract on blood pres-sure has been recognized to be, among others, a consequence ofits ability to inhibit the activity of angiotensin l-converting en-zyme (Hellstrom and others 2010; Sikora and others 2014). Thiseffect may be connected with protection of the coronary arter-ies (Bell and Gochenaur 2006) and heart muscle (Naruszewiczand others 2007) from ROS action. Due to its anti-inflammatoryproperties, A. melanocarpa fruit extract may be useful in the pro-tection of the human aorta from damage caused by inflammatoryprocesses, which was revealed in human aortic endothelial cells invitro (Zapolska-Downar and others 2012). Moreover, Daskalovaand others (2015) have reported that chokeberry juice protectsagainst atherogenesis in the aortic walls in aging rats. On this basisit can be concluded that A. melanocarpa juice may also protect el-derly people from atherogenic changes in the aorta and coronaryarteries, and in this way decrease the risk of heart infarction.

The results of studies with in vitro models on the influence ofA. melanocarpa berry extract on platelet activity, including humanplatelets, suggest that the protective effect of the extract may alsooccur in vivo. The extract from chokeberries has been noted to de-crease superoxide anion production in the platelets of patients withhypertension, hypercholesterolemia, and diabetes mellitus, as wellas of tobacco smokers, who are known to have an increased riskof cardiovascular diseases (Ryszawa and others 2006). Moreover, itprotected human platelets in vitro from oxidative and nitrative dam-ages induced by peroxynitrite (Olas and others 2008a). It has beenrevealed that chokeberry extract is more effective as an antiplateletfactor than resveratrol and grape seed extract (Olas and others2008b; Malinowska and others 2013). It reduced the changes inthe activities of SOD, GPx, and CAT in platelets in vitro subjectedto an impact of hydrogen peroxide (H2O2; Kedzierska and others2011). A. melanocarpa berry extract increased antiplatelet action of

human umbilical vein endothelial cells toward platelets activatedby adenosine diphosphate at a concentration of 5 µg/mL (Luzakand others 2010). Extract from berries of A. melanocarpa preventedclot formation and increased fibrin lysis in human plasma in vitrowith the model of induced hyperhomocysteinemia (Malinowskaand others 2012). The chokeberry extract (at concentrations of0.5, 5, and 50 µg/mL) prolonged clotting time, inhibited plateletaggregation, and thrombin-induced fibrinogen polymerization,and also decreased the maximal velocity of fibrin polymerizationand stabilized fibrin formation in the healthy human plasma invitro (Bijak and others 2011, 2013b). From an in vitro study it hasbeen found that aronia berry extract protects against peroxynitrite-induced nitrative damage to the fibrinogen in the human plasma,which has a positive impact on the process of blood clotting(Bijak and others 2013a). Moreover, Zapolska-Downar and oth-ers (2008) have reported that Aronox exerted protective actionagainst apoptosis in human umbilical vein endothelial cells treatedwith 7β-hydroxycholesterol, which may suggest that the extractfrom berries of A. melanocarpa can be effective in the preventionand treatment of atherosclerosis and damage to the blood vesselsinduced by cholesterol deposits.

It has been observed among human volunteers that the use ofA. melanocarpa berry extract may be effective in the prevention ofdisorders accompanied by metabolic syndrome and hypercholes-terolemia, as well as in the prevention of further progress of thesedisorders (Kowalczyk and others 2005; Broncel and others 2007;Duchnowicz and others 2012; Sikora and others 2012; Kardumand others 2015). The administration of 100 mg of Aronox (in theform of tablets) to 38 patients with metabolic syndrome 3 timesdaily for 1 or 2 mo resulted in an improvement of the lipid pro-file and normalization of hemostasis parameters such as fibrinogenlevel, maximum clotting time, plasma clotting time, clot stabi-lization time, fibrinolysis time, thrombin generation time, overallpotential of coagulation, as well as overall potential of clot for-mation and lysis (Sikora and others 2012). These effects can beexplained by the antioxidative action of the extract (Zapolska-Downar and others 2008; Duchnowicz and others 2012; Bijakand others 2013a). According to Duchnowicz and others (2012),a 2-mo supplementation with 100 mg of Aronox applied 3 timesper day to 25 patients with hypercholesterolemia decreased theconcentration of cholesterol in erythrocytes and protected fromheart infarction by preventing clot formation in the blood vessels.The administration of Aronox 3 times daily in the form of cap-sules containing 80 mg of anthocyanins for 30 d to 16 men withhypercholesterolemia increased the activities of catalase (CAT) andSOD, as well as the concentration of zinc (possessing antioxidativeproperties), and it decreased the concentrations of copper, Pb, andaluminum in erythrocytes (Kowalczyk and others 2005).

The consumption of aronia berries and their products, due tothe anti-inflammatory and antioxidative properties of their in-gredients, may decrease the levels of proinflammatory cytokinesand oxidized form of low-density lipoprotein (ox-LDL) in theserum protecting in this way from the occurrence of myocardialinfarction (Naruszewicz and others 2007). Naruszewicz and oth-ers (2007) have noticed that the administration of a chokeberryextract (in the form of capsules) for 6 wk to the patients aftermyocardial infarction treated with simvastatin or atorvastatin (20mg/day; cholesterol-lowering medications that block cholesterolproduction) for at least 6 mo resulted in a decrease in the concen-trations of inflammatory markers (8-isoprostanes and monocytechemoattractant protein-1) and ox-LDL in the serum. Moreover,the systolic and diastolic blood pressure was decreased by a mean of



11 and 7.2 mm Hg, respectively, in the group of patients adminis-tered with the aronia extract under the treatment with simvastatinor atorvastatin in comparison with the patients receiving placeboinstead of the chokeberry extract (Naruszewicz and others 2007).The administration of a chokeberry extract (in the form of cap-sules) in a dose of 100 mg 3 times daily for 6 wk has been reportedto decrease the systolic and diastolic blood pressure, as well as thelevel of oxidative stress and to inhibit cytokine-induced inflamma-tory response in a group of 13 patients with coronary artery diseaseafter myocardial infarction (Naruszewicz and others 2003). More-over, due to the presence of chlorogenic acid, juice and extractmade from chokeberries are capable of improving the lipid profileand regulating glucose levels in the blood of patients suffering fromhypercholesterolemia and metabolic syndrome (Broncel and others2007; Skoczynska and others 2007). Skoczynska and others (2007)have reported that regular drinking of chokeberry juice (250mL/24 h) for 6 wk by 58 men with mild hypercholesterolemiaresulted in a decrease in the systolic blood pressure by an averageof 13 mm Hg and diastolic blood pressure by a mean of 7 mmHg, decreased the concentrations of total cholesterol, low-densitylipoprotein (LDL) cholesterol, triglycerides, and glucose, as well asincreased the level of HDL cholesterol in the serum. The adminis-tration of 100 mg of aronia extract (in the form of tablets) 3 timesdaily for 2 mo to 25 patients with metabolic syndrome improvedtheir body mass index (BMI), decreased the systolic and diastolicblood pressure, as well as decreased the serum concentrations ofendothelin-1, total cholesterol, LDL cholesterol, and triglycerides,and also improved the oxidative/antioxidative status of erythro-cytes (Broncel and others 2007, 2010). The daily consumption of200 mL of chokeberry juice for 4 wk by 23 patients with stage 1hypertension decreased their systolic and diastolic blood pressureand improved the serum lipid status (Kardum and others 2015).Poreba and others (2009) have reported that drinking of choke-berry juice by 35 men with mild hypercholesterolemia improvedendothelial function and their lipid metabolism. The proven ef-fectiveness of chokeberry products in the treatment of metabolicsyndrome and hypercholesterolemia allows for the assumption thatthey may also play a role in the prevention of these disorders.

Basu and others (2010) recommended chokeberries and otherberries rich in polyphenols (cranberries and blueberries) as es-sential parts of a heart-healthy diet. So far there is a lack of anaccurately recommended dose of chokeberry products that shouldbe consumed daily for protection of the circulatory system. How-ever, taking the above results into account it can be concluded thatthe intake of 100 mg chokeberry extract (in the form of capsules ortablets) 3 times daily for 2 mo may be effective for improvement ofthe serum lipid profile and hemostatic parameters in patients withmetabolic syndrome (Duchnowicz and others 2012; Sikora andothers 2012). Moreover, the available literature data (Skoczynskaand others 2007; Kardum and others 2015) indicated that drink-ing 200 to 250 mL chokeberry juice per day for 4 to 6 wk maydecrease the blood pressure of patients with hypertension.

CancersStudies with animal models and in vitro models show that choke-

berry extracts and other products made from aronia fruit are ef-fective in the prevention of carcinogenic occurrences due to theirstrong antioxidative action (Gasiorowski and others 1997; Malikand others 2003; Zhao and others 2004; Lala and others 2006;Bermudez-Soto and others 2007a,b; Shih and others 2007; Olasand others 2010; Balansky and others 2012; Kedzierska and others2012, 2013a,b; Rugina and others 2012; Sharif and others 2012;

Li and others 2014; Pratheeshkumar and others 2014; Thani andothers 2014). The anticarcinogenic effect of aronia berry productsis related to the antioxidative properties of polyphenolic com-pounds which protect healthy cells from oxidative damage inducedby free radicals (Shih and others 2007), pro-apoptotic action whichenables the death of cells with carcinogenic changes (Rugina andothers 2012; Sharif and others 2012), and the ability to arrest thecell cycle of tumor cells (Malik and others 2003; Zhao and oth-ers 2004; Bermudez-Soto and others 2007a,b; Sharif and others2012). Polyphenolic compounds that were considered to be ac-tive against human acute lymphoblastic leukemia Jurkat cells arechlorogenic acid, cyanidin glycosides, and quercetin derivativesthat are able to induce apoptosis (Sharif and others 2012).

Chokeberry extract has pro-apoptotic properties (Sharif andothers 2012; Thani and others 2014). Cyanidin glycosides isolatedfrom aronia fruit extract have been reported to induce an accu-mulation of peroxides in HeLa tumor cell culture which triggersapoptotic pathways in these cells (Rugina and others 2012; Sharifand others 2012). The proven beneficial action of chokeberry juiceon human cancer cells is an argument which suggests the anticar-cinogenic effectiveness of chokeberry products in humans. Thiseffect has been observed on human acute lymphoblastic leukemiaJurkat cell line, human acute lymphoblastic leukemia Molt-4 cellline, human T cell lymphoblast-like cell line, and T leukemiacell line (HSB-2; Shariff and others 2012). A. melanocarpa juicecontaining 7.15 g of polyphenols per liter decreased the mito-chondrial membrane potential and released cytochrome c intothe cytoplasm in the acute lymphoblastic leukemia Jurkat cell lineand in human leukemia, but not in human healthy primary T-lymphocytes (Sharif and others 2012). The pro-apoptotic activityof chokeberry juice is connected with the ability of polyphenoliccompounds present in the aronia berries to inhibit cell proliferationby the cell cycle arrest in G2/M phase, upregulate the expressionof tumor suppressor p73, and activate caspase-3 (Sharif and oth-ers 2012). The 24-h treatment with chokeberry extract inhibitedthe growth of human HT-29 colon cancer cells by blocking thecell cycle at G1/G0 and G2/M phases, increasing the expressionof the cyclin-dependent kinase inhibitors (p27KIPI and p21WAFI),and decreasing the expression of cyclin A and B genes, as wellas by decreasing cyclooxygenase-2 gene expression (Malik andothers 2003). Chokeberry extract is able to specifically inhibit thegrowth of colonic cancer, but not NCM460 epithelial cells de-rived from the healthy colon (NCM460 cells; Malik and others2003; Zhao and others 2004). It has been revealed that choke-berry extract is a stronger inhibitor of the colon-cancer-derivedHT-29 cells than extract from a grape and bilberry (Zhao andothers 2004). The HT-29 cell growth was inhibited (by about50%) after a 48-h treatment with the chokeberry extract contain-ing 25 µg of anthocyanins per mL, while the grape extract waseffective only at a concentration of 75 µg anthocyanins per mL,and inhibited cell growth by 35% after a 48-h treatment (Zhao andothers 2004). The bilberry extract was effective at a concentrationof 25 µg of anthocyanins per mL and after a 48-h treatment itinhibited the HT-29 cell growth only by 25% (Zhao and others2004). The anticancer properties of chokeberry juice were alsonoted in the human colon cancer Caco-2 cells, where the juiceinhibited cell proliferation (by 30% to 40%) and viability (by 20%).The inhibition of cell proliferation by chokeberry juice may beconnected with arresting the cell cycle in the G2/M phase, up-regulating tumor suppressor carcinoembryonic antigen-related celladhesion molecule 1 (whose expression is reduced in the major-ity of early adenomas and carcinomas; Bermudez-Soto and others



2007a,b), as well as with downregulating genes related to tumorinvasion and metastasis such as fibroblast growth factor receptor2 and S100 calcium-binding protein A4 secreted by tumor andstromal cells (S100A4; Bermudez-Soto and others 2007a). Ac-cording to Abdullah Thani and others (2012) chokeberry extractmay exert anticancer action via induction of necrosis. They havenoted that the extract has exerted stronger anticancer propertiesto glioblastoma cell line U373 than curcumin, what has been re-vealed based on the half maximal inhibitory concentration (IC50;which describes the effectiveness of a substance in inhibiting abiological or biochemical function; Abdullah Thani and others2012). The IC50 value for chokeberry extract in glioblastoma cellline U373 was 200 µg/mL, while for curcumin only 15 µg/mL(Abdullah Thani and others 2012). Moreover, A. melanocarpa ex-tract causes downregulation of expression of matrix metallopro-teinases (MMP-2, MMP-12, MMP-16, MMP-17) in the U373cell line (Abdullah Thani and others 2012).

The available results of experimental studies suggest thatpolyphenolic compounds from chokeberries may prevent the de-velopment of skin cancers (Li and others 2014; Pratheeshkumarand others 2014). Li and others (2014) have revealed in vitro thatchlorogenic acid suppresses melanogenesis in B16 melanoma cells.Moreover, the research performed with an animal model (SKH-1 hairless mice) indicated that aronia fruit polyphenols protectagainst oxidative damage induced by ultraviolet B radiation (UVBradiation) in the skin (Pratheeshkumar and others 2014).

It should be emphasized that chokeberry extract supports theaction of anticancer drugs used in the treatment of some typesof cancer. For example, Thani and others (2014) have revealedthat the extract increased the effectiveness of gemcitabine againstgrowth of the pancreatic cell line (AsPC-1 cell line). Moreover,based on the available data, it can be concluded that the con-sumption of chokeberry products may be effective for the pro-tection against side effects of drugs used in chemotherapy (suchas cisplatin). The protective antioxidative effect of the extractand juice from chokeberries on healthy cells was noticed duringand after chemotherapy (Olas and others 2010; Kedzierska andothers 2012, 2013a,b; Valcheva-Kuzmanova and others 2013a).The mechanisms of antimutagenic and anticarcinogenic action ofchokeberry products as well as their cytoprotective influence onhealthy cells obtained from patients during and after chemotherapywith these products are described below. Valcheva-Kuzmanova andothers (2013a) have confirmed the cytoprotective effect of juicemade from A. melanocarpa fruit in the human embryonic kidneycell line HEK293T treated with cisplatin. Aronox at a concen-tration of 50 µg/mL decreased the level of oxidative stress inplatelets ex vivo without neoplastic changes obtained from patientswith invasive breast cancer during chemotherapy (Kedzierska andothers 2012), and it significantly reduced ex vivo the intensityof oxidative stress and changes of hemostasis in the plasma ofbreast cancer patients after surgery and the different phases ofchemotherapy (Kedzierska and others 2013b). It is important tounderline that chokeberry extract exerts antioxidative action insubjects with breast cancer (Olas and others 2010; Kedzierskaand others 2013a). The administration of chokeberry extract(50 µg/mL) to patients affected by breast cancer restored thelevels of low-molecular-weight thiols (physiological free radicalscavengers) in the plasma back to the level in healthy subjects(Olas and others 2010; Kedzierska and others 2013a). However,the extract had no influence on the activity of antioxidative en-zymes in the plasma from these patients during the different phasesof chemotherapy (Kedzierska and others 2013a).

Apart from aronia berries, aronia leaves may also be effec-tive in the protection and treatment of cancers. The findingby Skupien and others (2008) suggests that extract from aronialeaves may be effective against leukemia, including leukemia re-sistant to chemotherapy. Polyphenolic compounds present in theextract from A. melanocarpa leaves have been active in vitro inhuman promyelocytic-sensitive leukemia HL60 cell line and inmultidrug-resistant promyelocytic leukemia cells resistant to vin-cristine (HL60/VINC) and human promyelocytic leukemia cellsresistant to doxorubicin (HL60/DOX) sublines (Skupien and oth-ers 2008). However, up till now the antileukemic activity of thearonia leaves extract was revealed only in an in vitro model. Furtherresearch studies on this matter with in vivo models are needed toexplain the possible role of the extract in humans suffering fromleukemia resistant to chemotherapy.

Taking the above into account it can be supposed that extractsfrom aronia berries and probably from aronia leaves are effective inthe prevention of the development of cancers as well as in cancertreatment. However, up to now there has been no evidence thatchokeberry products may prevent or even be used for the effectivetreatment of cancers in humans. Thus, further investigations in thismatter are necessary. Moreover, it is important to underline thatchokeberry extract (at a concentration of 50 mg/mL) has beenrevealed to protect healthy cells of patients with invasive breastcancer from the oxidative stress developing during chemotherapy,and it may be recommended for this purpose.

Digestive system disordersThe available literature data show that products prepared from

A. melanocarpa berries may also be useful in the protection againstdigestive tract disorders, such as nonalcoholic fatty liver disease(NAFLD), which is a very common digestive system disorder(Boncheva and others 2013; Wang and others 2015). The positiveimpact of Aronia melanocarpa extract and juice on digestive systemresults from their antioxidative properties (Valcheva-Kuzmanovaand others 2005; Wang and others 2015).

The in vitro treatment with chokeberry extract of HepG2 cells,in which changes specific to NAFLD were induced by oleic acid,resulted in a decrease in ROS formation and triglyceride accumu-lations in these cells (Wang and others 2015). The beneficial im-pact is probably connected with the action of cyanidin 3-glucosidepossessing an ortho-hydroxyl group (-OH) in its B ring, which isprobably able to bind with triglycerides decreasing their accumu-lation in hepatocytes (Wang and others 2015).

The studies performed in animal models show that choke-berry juice administration may decrease the development of gas-tric ulcers (Valcheva-Kuzmanova and others 2005; Wroblewskaand others 2008) and NAFLD (Park and others 2016). Valcheva-Kuzmanova and others (2005) have reported that A. melanocarpafruit juice decreased the level of malondialdehyde (MDA), beinga biomarker of lipid peroxidation, in the plasma and gastric mu-cosa and diminished the size of gastric ulcers and their incidence.Chokeberry juice added to diets of rats for 4 wk, in doses corre-sponding to the daily intake in human of about 0.5, 1, and 2 Lof juice, increased the pH in the stomach, which protected fromthe development of peptic ulcer disease as well as decreased theconcentration of triglycerides and total cholesterol in the serum,which in turn may decrease the risk of cirrhosis (Wroblewska andothers 2008). Park and others (2016) have revealed that an admin-istration of chokeberry powder (at concentrations of 0.5% and 1%)for 8 wk to mice with high-fat diet (containing 41% of energy)can attenuate the expression of genes for fatty acid synthase, sterol



regulatory element-binding protein, and acetyl-CoA carboxylasein the liver. Enhanced expression of these genes contributes toNAFLD development (Nagaya and others 2015). Moreover, thischokeberry powder decreased the concentrations of triglyceridesand the size of the fat droplets in hepatocytes (Park and others2016).

Boncheva and others (2013) have revealed that the daily admin-istration of 200 mL of A. melanocarpa fruit juice (divided into 3portions—each of them was given 20 min before a meal) for 60 d tothe patients suffering from NAFLD, and applying a healthy lifestyleprogram more effectively improved the liver function (evaluatedbased on the serum activities of the liver marker enzymes), carbo-hydrate metabolism (including fasting blood glucose, basal insulin,and HbA1c), and lipid parameters in the serum (total cholesterol,HDL and LDL cholesterol, triglycerides, apolipoprotein A1, andapolipoprotein B).

According to our knowledge, there is a lack of information inthe available literature concerning effectiveness of A. melanocarpaberries and their products in protection from inflammatory boweldisease. This issue requires to be studied.

Overweight and obesityExcessive body weight is an important public health problem

in industrialized countries. Overweight means a BMI equal to orgreater than 25 kg/m2, while obesity occurs when a BMI is equalto or greater than 30 kg/m2 (World Health Organization 2015).According to WHO, in 2014, 39% of adults all over the world wereoverweight, of which 13% were obese, whereas in 2013, 42 mil-lion children under the age of 5 were overweight or obese (WorldHealth Organization 2015). Overweight and obesity are the ma-jor risk factors for noncommunicable diseases, especially diabetesand cardiovascular diseases, osteoarthritis, and some cancers (espe-cially endometrial, breast and colon; World Health Organization2015).

Some literature data indicate that A. melanocarpa berries maybe useful in the prevention of development of overweight andobesity (Shin and Jung 2016). The possible protective impact ofA. melanocarpa extract in prevention of obesity and overweightis connected with antioxidative properties (Zielinska-Przyjemskaand others 2007; Shin and Jung 2016). It has been revealed thata chokeberry extract (at concentrations of 0.5 and 1 mg/mL) inpreadipocyte cell line 3T3-L1 cells inhibited adipogenesis (a pro-cess of formation of fat cells and fatty tissue) by down regulationof adipokine-specific genes (such as genes of leptin, adiponectin,monocyte chemoattractant protein-1 relative to nontreatedadipocytes, lipoprotein lipase, peroxisome proliferator activatedreceptor gamma, fatty acid-binding protein, and glyceraldehyde3-phosphate dehydrogenase; Shin and Jung 2016). Moreover, thisextract decreased the expression of the key adipocyte differenti-ation regulator peroxisome proliferator-activated receptor-γ andthe fatty acid binding protein 4 gene during the differentiation ofpreadipocytes into adipocytes (Shin and Jung 2016).

Zielinska-Przyjemska and others (2007) have revealed that invitro treatment of neutrophils obtained from obese patients withjuice from A. melanocarpa berries decreased the extent of oxidativedamages and apoptosis.

The abdominal obesity is a risk factor of the metabolic syndromeand about two-thirds of the people with abdominal obesity exhibitthe metabolic syndrome (Aristizabal and others 2016). A possibleuse of the aronia extract in human suffering from metabolic syn-drome is discussed by us in the chapter entitled “Diabetes.”

Other health problemsChokeberries can also be used for the prevention and treat-

ment of other health problems: colds, some skin troubles causedby inflammatory processes, and disorders of the reproductive andnervous systems (Pawłowicz and others 2000, 2001; Hellstrom andothers 2010; Sonoda and others 2013; Savikin and others 2014;Eftimov and Valcheva-Kuzmanova 2014a,b; Valcheva-Kuzmanova2014).

It was revealed in animal models that chokeberry juice ex-erts antidepressant- and anxiolytic-like effects during exposure toethanol, or to constant light, and under social isolation, whichwas confirmed in behavioral tests and reflected in increased loco-motor activity and decreased immobility time in the forced swimtest (Eftimov and others 2014; Eftimov and Valcheva-Kuzmanova2014a,b; Valcheva-Kuzmanova 2014). The beneficial impact onthe central nervous system is supposed to be connected with theability of polyphenolic compounds to cross the blood–brain bar-rier and to prevent oxidative stress development in the brain andnonadaptive responses to stress as well as to modulate monoamin-ergic neurotransmission (Valcheva-Kuzmanova 2014).

In the past chokeberries were used for the treatment of coldsamong Native Americans (Hellstrom and others 2010). The effec-tiveness of aronia in the treatment of colds probably results fromthe ability of some compounds present in this fruit to regulatethermogenesis by increasing the level of noradrenaline that de-creases an excessive body temperature (Sonoda and others 2013).Sonoda and others (2013) have reported that A. melanocarpa ex-tract administered for 4 wk at a dose of 150 mg/day (in a form oftablets; each containing 50 mg of A. melanocarpa extract) regulatedthermogenesis in healthy women with a cold constitution.

Chokeberry extract may probably be useful in the preventionagainst reproductive system disorders due to its antioxidative prop-erties (Pawłowicz and others 2000, 2001). It is well known thatoxidative stress is one of the main mechanisms leading to infertilityin males and that an excessive ROS amount can affect the spermquality and lead to a significant decrease in the number of sper-matozoids (Kefer and others 2009). Treatment with chokeberryextract decreased oxidative stress intensity in the blood of mensuffering from oligospermia, and it increased the concentrationof fructose (a marker of the function of seminal vesicles in infer-tile men) in their semen (Pawłowicz and others 2001). Moreover,the administration of the extract decreased ox-LDL concentrationin the serum (a marker of lipoprotein-associated oxidative stress)of women during pregnancy complicated by intrauterine growthretardations (Pawłowicz and others 2000).

The Possibility of Using Chokeberries in CosmeticProducts

Owing to the multidirectional beneficial action of chokeberryingredients, these berries are also used in cosmetology. Consumerpopularity of cosmetics made from natural substances has beengrowing in many countries (Aburjai and Natsheh 2003; Gediyaand others 2011). However, there are no comprehensive data sug-gesting that the use of cosmetics containing A. melanocarpa berryextract has a positive impact on human skin, but according toSavikin and others (2014) drinking of chokeberry juice decreasescellulite. So far the use of aronia berries for the production ofcosmetics is based on the results of experimental in vivo and in vitrostudies providing evidence for the beneficial impact of compoundspresent in A. melanocarpa berries (Savikin and others 2014; Youngand Young 2015).



Polyphenolic compounds present in chokeberries are absorbedinto the skin where they exert anti-aging and anti-allergic ac-tion connected with their anti-inflammatory and anti-oxidativeproperties. Young and Young (2015) have revealed that choke-berry extract is well absorbed through human skin cells, and thatnanoparticles made with lecithin and encapsulated chokeberry ex-tract are even better absorbed due to their small size. Yutani andothers (2014) have noticed in vitro that chlorogenic acid is welldistributed in the epidermis, while, according to Marti-Mestresand others (2007), chlorogenic acid and caffeic acid are well dis-tributed in all layers in the skin model. Moreover, dal Belo andothers (2009) have found that quercetin penetrates into the epider-mis. These findings confirm that polyphenolic compounds presentin chokeberries are absorbed into the skin where they then exerttheir action.

An extract from A. melanocarpa berries has been revealed tohave anti-inflammatory action on human dermal cell line (Youngand Young 2015). It is important to stress that polypheno-lic compounds present in chokeberries protect the skin fromUVB radiation (Gabrielska and others 1999; Li and others 2014;Pratheeshkumar and others 2014), and thus the aronia extract canbe used for the production of cosmetics protecting from UVBradiation (Gabrielska and others 1999). Data obtained in animalmodels suggest that polyphenol present in chokeberries, such ascyanidin 3-glucoside and caffeic acid, protect the skin from oxida-tive damage, inflammation, and the development of skin cancersinduced by exposure to UVB radiation (Pratheeshkumar and oth-ers 2014). Moreover, it has been revealed that chlorogenic acid,which is one of the most abundant polyphenols in chokeberries,suppresses melanogenesis in B16 melanoma cells in vitro (Li andothers 2014).

The study by Young and Young (2015) suggests that chokeberryextracts may be more effective in skin protection when they areadded to cosmetics in the form of nanoparticles because they canpenetrate the skin more deeply. It has been revealed that nanocap-sules (100 to 200 µm in diameter) made with lecithin and encap-sulated extract of A. melanocarpa berries possess high antioxidativeactivity, an ability to inhibit hyaluronidase activity in CCD-986skhuman dermal fibroblasts, and strong anti-inflammatory properties(Young and Young 2015). These nanoparticles inhibited nitric ox-ide (NO) production in RAW264.7 cells and decreased secretionof IL-6 and TNF-α from human Jurkat T cells (Young and Young2015). Moreover, Young and Young (2015) have revealed that 70%ethanolic extract of A. melanocarpa berries encapsulated with anedible encapsulant lecithin exerted stronger anti-inflammatory ac-tion in human dermal cell lines than a classical ethanolic extract ofaronia fruit because this extract is better absorbed in the form ofnanoparticles through cellular membranes. On this basis it may beconcluded that the chokeberry extract encapsulated with lecithinnanoparticles is better absorbed through the human skin and thatthis formulation could probably be used as an effective ingredientof anti-inflammatory cosmetics.

The data on the effectiveness of chokeberry juice in the treat-ment of cellulite allow the assumption that chokeberries maybe used for the production of anticellulite products (Savikin andothers 2014; Young and Young 2015). This assumption is based onthe reported effectiveness by Savikin and others (2014) of choke-berry juice in women with cellulite. The daily consumption of100 mL of chokeberry juice for 90 d by 29 women (aged 25 to48) with a grade 2 cellulite resulted in a reduction in the lengthof subcutaneous tissue fascicles in 97% of the subjects and in the

subcutaneous tissue thickness as well as in the disappearance ofedema in all subjects (Savikin and others 2014).

Cosmetics made from aronia are recommended for dry allergicskin with dilated breaking capillaries, the improvement of micro-circulation, a decrease in the inflammatory state of the skin as wellas for a delay of the process of skin aging. These products are avail-able on the market as moisturizing and antiwrinkle creams, facetonics, body balms, lip balms, soaps, and hand creams (described as“Aronia cosmetics”). Chokeberries are a valuable raw material forthe production of cosmetics for skin redness and erythema due tothe high content of anthocyanins. Taking into account the grow-ing interest in natural products, it seems possible that, in the future,A. melanocarpa will be widely used for cosmetology purposes.

The Possibility of Using A. melanocarpa Berries andTheir Products in the Protection and Treatment of theAdverse Health Effects of Exposure to Xenobiotics

Increasing the use of numerous chemical substances in industrialand daily products, and thus causing humans to be exposed to var-ious substances dangerous to health, has attracted growing interestin the possible ways of protection from the unfavorable effects oftheir action as well as the treatment of diseases caused by them.The knowledge on the wide spectrum of beneficial actions of theingredients of aronia berries and their products, as well as the ex-planation of the mechanisms of toxicity of numerous xenobiotics,has aroused the interest of scientists who have been focusing onthe possibility of using aronia berries and their products in pre-venting the toxic action of some xenobiotics and counteractingunfavorable health effects caused by them.

The 1st scientific report about the possibility of the protectiveuse of aronia berries during exposure to xenobiotics was pub-lished by Niedworok and others (1995). The authors reportedthat anthocyanins present in chokeberry extract protected fromoxidative stress in the erythrocytes of rabbits caused by cyclophos-phamide (an anticancer alkylating drug) and protected healthy cellsfrom a decrease in the activities of antioxidative enzymes duringchemotherapy. The number of reports on the beneficial impactof products of A. melanocarpa berries and particular polyphenoliccompounds present in them under exposure to various substanceshas been increasing from year to year (Braun and others 2011;Kujawska and others 2011; Prabu and others 2011; Szaefer andothers 2011; Balansky and others 2012; Krishnakumar and others2012; Brzoska and others 2013, 2015a,b, 2016b; Roszczenko andothers 2013; Wang and others 2013; Dietrich-Muszalska and oth-ers 2014; Khandelwal and Abraham 2014; Koriem and Soliman2014; Navaneethan and Rasool 2014; Papiez and Krzysciak 2014;Podder and others 2014; Qader and others 2014; Hao and others2015; Hu and others 2015).

Due to the fact that polyphenols are characterized by strong an-tioxidative properties and that they are abundant in -OH groups,which not only scavenge ROS (Foley and others 1999; Iwa-hashi 2000; Lodovici and others 2001; Denev and others 2012;Braunlich and others 2013c), but are also capable of forming com-plexes with metals resulting in their inactivation (Smith and others2000; Adams and others 2002; Cornard and Merlin 2002; Boi-let and others 2005; Cornard and Lapouge 2006; Cornard andothers 2008; Okoye and others 2013; Jayantakumar and Shukla2014; Ravichandran and others 2014; Figure 6), much attentionhas been paid to the possibility of using aronia berries for the pre-vention against harmful health effects caused by xenobiotics pos-sessing pro-oxidative properties, including metals (Figure 5). Since



Figure 6–Possible mechanisms of protective action of the berries of Aronia melanocarpa against xenobiotics toxicity.

anthocyanins have been reported to be capable of penetrating intovarious organs of rats, including target organs for xenobiotics,such as liver, kidney, brain, and heart (Felgines and others 2009;Kirakosyan and others 2015), it seems that these compounds mayexert their direct antioxidative action in these organs.

Until now, the protective effects of A. melanocarpa berriesand products made from them have been described in regard toheavy metals, such as Cd (Brzoska and others 2013, 2015a,b,2016a,b; Kowalczyk 2003b; Roszczenko and others 2013) and Pb(Kowalczyk and others 2002, 2003a), ethanol (Niedworok andothers 1997; Matsumoto and others 2004; Valcheva-Kuzmanovaand others 2013b, 2014), carbon tetrachloride (CCl4; Valcheva-Kuzmanova and others 2004), N-nitrosocompounds (Atanasova-Goranova and others 1997; Kujawska and others 2011),PAH (benzo-[a]-pyrene and 7,12-dimethylbenz[a]anthracene;Gasiorowski and others 1997; Szaefer and others 2011), sulphide-2-chloroethyl-3-chloropropyl (Kowalczyk and others 2004),

2-amino fluorine (Gasiorowski and others 1997), sulfur mustard(Kowalczyk and others 2004), and some medicines (Niedworokand others 1995; Valcheva-Kuzmanova and others 2005, 2013a,2014; Dietrich-Muszalska and others 2014; Figure 5). Moreover,A. melanocarpa extract has been reported to protect from theharmfulness of tobacco smoke (Balansky and others 2012).Apart from that, a protective effect of some polyphenoliccompounds present in chokeberries, such as chlorogenic acid,quercetin, kaempferol, caffeic acid, p-coumaric acid, cyanidin,and pelargonidin, has been revealed regarding the chosen effectsof toxic action of Cd (Morales and others 2006; Vicente-Sanchezand others 2008; Renugadevi and Prabu 2010; Prabu and others2011; Krishnakumar and others 2012; Wang and others 2013;Navaneethan and Rasool 2014; Hao and others 2015), Pb (Liuand others 2010a), ethanol (Molina and others 2003; Liu andothers 2010b), paraquat (Tsuchiya and others 1996; Park andothers 2010; Podder and others 2014), sulfur mustard (Kumar



and others 2001; Gautam and others 2007), methamphetamine(Koriem and Soliman 2014), diepoxybutane (Khandelwal andAbraham 2014), urethane (Khandelwal and Abraham 2014),tobacco smoke (Braun and others 2011), and some medicines(Kuhlmann and others 1998; Papiez and Krzysciak 2014; Qaderand others 2014; Hu and others 2015). These findings provideconfirmation of the effectiveness of aronia berry products as wellas help to explain, at least partially, the possible mechanisms of thepositive impact of A. melanocarpa products regarding the toxicityof xenobiotics. Unfortunately, the data on the beneficial action ofchokeberries and polyphenolic compounds present in them orig-inate only from in vivo studies performed in animal models (rats,mice, and rabbits) and from in vitro experiments. The investigationsconcerning the influence of the consumption of various choke-berry products on the human organism during environmental andoccupational exposure to toxic substances as well as the subjectspoisoned by these substances are still lacking. However, the useful-ness of A. melanocarpa products and aronia-occurring polyphenoliccompounds in counteracting the toxicity of various xenobioticsrevealed in experimental studies allow to hypothesize about theirpossible effectiveness also in humans and show the necessity ofwell-planned epidemiological studies on this issue, including, firstof all, investigations among subjects exposed to the substances forwhich aronia effectiveness has been revealed in animal models.

Toxic heavy metalsToxic heavy metals are the main chemical contaminants of the

natural and occupational environment and of food (Echeverry andothers 2015; Mok and others 2015; Newbigging and others 2015).An important source of intoxication with these metals is also activeand passive tobacco smoking (Talio and others 2010; Leung andothers 2013). Thus, most of the general population is exposed tothese harmful elements for a lifetime.

It is important to emphasize that toxic heavy metals, especiallyCd and Pb, are characterized by strong cumulative properties inthe human and animal organisms. These elements easily enter thecells where they are retained for a long time in a form bound withvarious biomolecules (Singh and others 2011). Thus, an effectiveway of protection from retaining the absorbed metals in the bodyand from their toxic action, as well as the treatment of poisoningscaused by them, should consist of their removal from the cellsand elimination from the organism. Various synthetic compoundscapable of chelating metals (such as 2,3-dimercaptopropanol –British antilewisite – BAL, 2,3-dimercaptopropane-1-sulfonic acid– DMPS, and 2,3-dimercaptosuccinic acid – DMSA) have beendesigned to remove toxic metals from the sites of their binding incells and to facilitate their elimination from the body via excretionwith the urine in the form of chelated complexes (Blaurock-Buschand Busch 2014). However, so far there are no effective therapiesfor body purification from heavy metals.

Because of the ubiquitous exposure to heavy metals and theirhigh toxicity creating a risk of occurrence of harmful effects evenat low exposure (Ferraro and others 2010; Liu and others 2013;Wallin and others 2014), many efforts have been undertaken tofind harmless substances which may effectively protect from metalaccumulation in the organism. Taking into account that for thenonsmoking general population food is the main source of expo-sure to heavy metals, the attention of scientists has been focusedon the substances capable of decreasing the gastrointestinal absorp-tion of toxic metals (Ferraro and others 2010; Chen and others2013; Tellez-Plaza and others 2013; Akesson and others 2014;Sommar and others 2014; Wallin and others 2014; Echeverry and

others 2015; Mok and others 2015; Newbigging and others 2015;van Maele-Fabry and others 2016). The presence of -OH groupsin the structure of polyphenolic compounds and the antioxida-tive properties of these compounds have focused the attentionof scientists on the possibility of protective use of polyphenol-rich plant products, including chokeberries, during exposure toCd and Pb, which possess pro-oxidative properties. The com-plexation of toxic metals by polyphenols is possible due to thepresence of 3′,4′-dihydroxyl groups in the B ring, as well as be-tween the 3-hydroxyl and 4-carbonyl groups in the C ring andbetween 5-hydroxyl group in the A ring and 4-carbonyl group inthe C ring (Smith and others 2000). The available literature dataindicate that polyphenolic compounds present in chokeberries,such as caffeic acid, chlorogenic acid, quercetin, and cyanidin,may form complexes not only with Cd and Pb, but also withaluminum and chromium (Smith and others 2000; Adams andothers 2002; Cornard and Merlin 2002; Boilet and others 2005;Cornard and Lapouge 2006; Cornard and others 2008; Okoye andothers 2013; Jayantakumar and Shukla 2014; Ravichandran andothers 2014). Cd has been complexed by quercetin using in vitromodels (Ravichandran and others 2014) and also cyanidin agly-con (Okoye and others 2013; Jayantakumar and Shukla 2014)at concentrations ranging from 112 to 5600 µg/L. These con-centrations are higher than the concentrations determined in theblood of the general population in unpolluted areas (0.2 to 0.65µg/L—in nonsmokers; in smokers they are higher on average byseveral times; Kira and others 2015) as well as smoking (41.5 to67.5 µg/L; Nishijo and others 2014) and nonsmoking inhabitants(1.7 to 7.3 µg/L; Nishijo and others 2014) of polluted areas.

Pb has been complexed in in vitro models by cyanidin aglycon(Okoye and others 2013; Jayantakumar and Shukla 2014), caffeicacid (Boilet and others 2005), and chlorogenic acid (Cornard andothers 2008) at Pb concentrations from 207 to 103500 µg/L.These concentrations are markedly higher than the ones noticedin the blood of the general population (29 to 33 µg/L; Kira andothers 2015), but are similar to (or even less than) the concentra-tions found in the blood of factory workers (397 ± 113.6 µg/L to787 ± 271.1 µg/L) and the concentrations present in the bloodof inhabitants of polluted area (50 to 430 µg/L; Ngwoke and oth-ers 2015). The above findings seem to indicate that polyphenoliccompounds present in aronia berries may complex these met-als in the gastrointestinal tract preventing their absorption. Sincepolyphenolic compounds are present in the general circulation(de Ferrars and others 2014) and are capable of penetration intoorgans, which may be damaged by heavy metals (kidney, liver,brain, and heart; Felgines and others 2009; Kirakosyan and oth-ers 2015), it seems possible that these compounds may also bindions of metals already absorbed into the organism and in this wayprevent their toxic action and facilitate their elimination from thesites of action and storage, and accelerate their excretion fromthe body. Thus, it may be supposed that chokeberries may beused by people environmentally exposed to Cd and Pb as wellas by factory workers to decrease the absorption of these toxicmetals from the gastrointestinal tract and to diminish their distri-bution into various organs via blood (de Ferrars and others 2014;Kirakosyan and others 2015); however, this issue needs furtherstudies.

In the available literature, there are numerous data on the protec-tive impact of polyphenolic compounds present in various naturalproducts under exposure to these metals (Ferraro and others 2010;Chen and others 2013; Tellez-Plaza and others 2013; Akessonand others 2014; Sommar and others 2014; Wallin and others



2014; Brzoska and others 2015a,b, 2016a,b; Echeverry and oth-ers 2015; Mok and others 2015; Newbigging and others 2015;Kopec and others 2016; van Maele-Fabry and others 2016); how-ever, data indicating the possibility of protective chokeberry useduring exposure to Cd and Pb are still sparse, so further researchon this matter is necessary. Especially warranted are epidemiologi-cal studies on the effectiveness of the consumption of aronia-madeproducts among humans exposed to toxic metals environmentallyand occupationally, including habitual tobacco smokers who aresimultaneously exposed not only to numerous toxic metals, butalso to a great number of other xenobiotics.

CdNumerous epidemiological studies provide evidence that

chronic, even relatively low, exposure to Cd, occurs in indus-trialized countries, which may be harmful to human health (Fer-raro and others 2010; Kalariya and others 2010; Shargorodsky andothers 2011; Chen and others 2013; Tellez-Plaza and others 2013;Akesson and others 2014; Sommar and others 2014; Wallin andothers 2014; Wu and others 2014; Bruning and others 2015; Byberand others 2015). Chronic environmental exposure to this metalhas been revealed to contribute to the development of osteoporo-sis (Chen and others 2013; Akesson and others 2014; Sommarand others 2014), cardiovascular diseases (Tellez-Plaza and others2013), and renal dysfunction (Ferraro and others 2010; Wallin andothers 2014; Byber and others 2015). Moreover, environmentalexposure to Cd may contribute to blindness (Kalariya and oth-ers 2010; Wu and others 2014) and hearing loss (Shargorodskyand others 2011; Choi and others 2012). Occupational exposureto this metal creates also the risk of respiratory system damage(Moitra and others 2013; Bruning and others 2015) and maylead to cognitive impairment (Draz and others 2009; Bruning andothers 2015). Moreover, Cd is a teratogenic and carcinogenic agent(Veeriah and others 2015; van Maele-Fabry and others 2016). Ithas been recognized that exposure of the general population tothis heavy metal in industrialized countries will show an increas-ing trend in future decades (Jarup and Akesson 2009; Nawrot andothers 2010). It is also important to underline that there is no safetymargin between the level of environmental exposure to Cd andthe threshold of harmful health effects caused by this xenobiotic(Jarup and Akesson 2009). Thus, Cd has attracted special atten-tion of researchers who investigate the possibility of using naturalsubstances in the protection from exposure to environmental pol-lutants. However, the available data on the possible protective roleof A. melanocarpa berries and their products, as well as particularpolyphenolic compounds present in aronia berries regarding thehealth effects of exposure to Cd, are very limited so far and comeexclusively from experimental studies, including mainly our owninvestigations.

The 1st suggestion that A. melanocarpa berries may play a role inthe prevention against Cd accumulation in the body and its toxic-ity was presented by Kowalczyk and others (2003b). The authorsrevealed that intragastric (by stomach tube) administration of anaqueous solution of anthocyanins from A. melanocarpa berries at adose of 10 mg/kg body weight (b.w.) to rats exposed to cadmiumchloride (CdCl2) at a dose of 4 µg CdCl2· 2½ H2O/kg b.w. for30 d decreased Cd accumulation in the liver and kidney (by about31% and 68%, respectively), as well as prevented a Cd-inducedincrease in the activities of aspartate aminotransferase (AST) andalanine aminotransaminase (ALT), and it restored the serum con-centrations of bilirubin and urea to the values of the control group(Kowalczyk and others 2003b). However, the 1st and only until

now wide-designed study indicating that A. melanocarpa berriesmay be used for the prevention against toxic action of Cd wasundertaken in our laboratory (Brzoska and others 2013, 2015a,b,2016b; Roszczenko and others 2013). In our study, the impact ofpolyphenol-rich chokeberry extract (commercial powdered ex-tract containing 65.74% of polyphenols) was evaluated in a ratmodel reflecting low and moderate lifetime human exposure toCd. For this purpose, this metal was administered in the diet atthe concentration of 1 mg Cd/kg (daily intake ranged between37.5 and 84.88 µg Cd/kg b.w.) or 5 mg Cd/kg diet (daily intakewas in the range from 196.69 to 404.76 µg Cd/kg b.w.) for upto 24 mo (Brzoska and others 2015a, 2015b). To monitor thedevelopment of Cd-induced changes under chronic intoxicationand the possible protective impact of the extract, all measurementswere performed after 3, 10, 17, or 24 mo. The assay of Cd con-centration in the blood and urine (main indices of exposure tothis metal) of the animals exposed to 1 mg Cd/kg diet (0.103 to0.324 µg/L and 0.085 to 0.354 µg/g creatinine, respectively) and5 mg Cd/kg diet (0.584 to 1.332 µg/L and 0.284 to 0.820 µg/gcreatinine, respectively; Brzoska and others 2015a) confirmed thatthe used levels for rats exposure corresponded well with the envi-ronmental human exposure in industrialized countries (Byber andothers 2015; Kira and others 2015; Motawei and Gouda 2015).The polyphenol-rich chokeberry extract was administered as a0.1% aqueous solution applied as the only drinking fluid (pro-vided daily from 41.5 to 104.6 mg of polyphenols/kg b.w.) aloneand under the exposure to Cd for up to 24 mo. The study wasperformed in a female rat model because Cd concentrations inwomen are higher than in men and females are more susceptibleto its toxic action (Chen and others 2013; Sommar and others2014; Motawei and Gouda 2015).

The results of the study conducted in the above-described ex-perimental model (Brzoska and others 2013, 2015a,b, 2016b;Roszczenko and others 2013) allowed to hypothesize that theconsumption of aronia fruit products may play an important pro-tective role. Administration of the 0.1% aqueous solution of thechokeberry extract under long-term exposure to Cd increased fe-cal and urinary excretion of this metal and decreased its apparentabsorption and retention in the body leading, as a result, to a lowerbody burden of this element. However, the protective influence ofthe extract on Cd metabolism depended on the level and durationof exposure to this metal. The administration of chokeberry ex-tract under an exposure to 1 mg Cd/kg diet had only a very slightprotective impact against the Cd body burden, whereas its appli-cation under the treatment with 5 mg Cd/kg diet significantlydecreased the apparent absorption and retention in the body, andincreased urinary excretion of this metal resulting in its lowerconcentration in the blood and lower accumulation in soft tissues(mainly in the liver and kidneys) and bone tissue. The extractadministration under the moderate 24-mo intoxication with Cddecreased the total pool of Cd in the liver and kidneys by 30%, andits total pool in internal organs by 20% to 29% (Brzoska and oth-ers 2015a). The decreased accumulation of Cd in the body mightresult from Cd complexation in the lumen of the gastrointestinaltract by polyphenolic compounds present in the chokeberry ex-tract, which decreased Cd bioavailability and absorption, as well asfrom its increased urinary excretion. These mechanisms are pos-sible due to the abundance of –OH groups in the structure ofpolyphenolic compounds (Hider and others 2001). The decreasedCd absorption and accumulation in the body may also be explainedby interactions between this toxic metal and other components ofchokeberries. The absorption of Cd through the gastrointestinal



tract may be decreased as a result of its competition with zinc fordivalent metal ion transporter (Illing and others 2012) and zinctransporters (Yang and Shu 2015). Zinc may compete with Cd forbinding sites in metallothionein (MT), which is a protein takingpart in the accumulation of metals as well as in their excretionfrom the body (Yang and Shu 2015). Moreover, pectins, dietaryfiber, cellulose, hemicellulose, and lignins (Table 2), which all maybind Cd in the gastrointestinal tract, thus preventing its absorptionand thereby decreasing retention of this xenobiotic in the body, arepresent in chokeberries (Borycka and Stachowiak 2008; Borycka2012).

Our study in the experimental model of life-time human ex-posure to Cd provided evidence that chokeberry extract offersimportant protection from skeleton damage which is, apart fromkidney damage, one of the critical effects of low chronic exposureto this heavy metal. The extract protected against Cd-induceddisturbances in the bone tissue metabolism (Brzoska and others2015b), improved the bone oxidative–antioxidative status (Brzoskaand others 2016b), and improved the bone biomechanical proper-ties, thus decreasing the risk of bone fractures (Brzoska and others2013). Administration of the extract completely prevented Cd-induced disorders in the bone mineral status (a decrease in thevolumetric bone mineral density of the femur and the contentof mineral components, especially calcium) at the distal femoralepiphysis of female rats (Brzoska and others 2015b). The extractrestored the levels of indices of bone formation (osteocalcin inthe serum, osteoprotegerin, and alkaline phosphatase – ALP inthe serum and bone tissue) and the concentrations of indices ofbone resorption (carboxy-terminal cross-linking telopeptides oftype I collagen in the serum and soluble receptor activator of nu-clear factor-κB ligand in the serum and distal femur epiphysis) tothe values in the control group, indicating its ability to preventCd-induced enhanced bone resorption and its inhibited forma-tion (Brzoska and others 2015b). The chokeberry extract-causeddecreased Cd accumulation in the bone tissue and the improve-ment of the bone metabolism had a positive impact on the bonebiomechanical properties. The administration of the extract pre-vented Cd-induced weakening of the biomechanical properties(yield strength, fracture strength, stiffness, and Young modulus ofelasticity) of the femoral neck and femoral diaphysis, and the 4thlumbar spine vertebral body after low and moderate prolongedexposure to Cd (Brzoska and others 2013; Roszczenko and others2013; unpublished data).

The results of our study allow to recognize that the bene-ficial impacts of the extract on the bone metabolism and thebone biomechanical properties are related, at least partially, to theimprovement of the bone oxidative/antioxidative status (Brzoskaand others 2016b). Oxidative/reductive processes are an integralcomponent of bone remodeling (Hubert and others 2014), andCd-induced disorders in the oxidative/reductive balance in thebone tissue are involved in the mechanisms of Cd-induced bonedamage (Chen and others 2013; Brzoska and others 2016b). Theadministration of aronia berry extract under the low and moder-ate chronic exposure to Cd improved the enzymatic antioxidativebarrier (estimated based on the activities of GPx, glutathione re-ductase – GR, CAT, and SOD) and protected from the accumu-lation of H2O2 in the bone tissue of the female rats under the lowand moderate exposure to Cd (Brzoska and others 2016b). Theadministration of aronia extract decreased total oxidative status(TOS), increased total antioxidative status (TAS), and decreasedthe level of oxidative stress (TOS/TAS) in the serum and bonetissue of the animals treated with Cd (Brzoska and others 2016b).

Moreover, administration of the extract provided significant pro-tection from Cd-induced lipid peroxidation (expressed as lipid per-oxides and F2-isoprostane concentrations) and oxidative damageto the protein (evaluated based on protein carbonyls concentra-tion) and DNA (evaluated based on 8-hydroxy-2′-deoxyguanosineconcentration-8-OHdG) in the bone tissue (Brzoska andothers 2016b). Numerous correlations noted between indicesof the oxidative/antioxidative bone status and markers of bonemetabolism in the animals receiving the extract from aronia berriesalone and under exposure to Cd confirmed the involvementof the antioxidative properties of chokeberries in the mecha-nisms of their osteoprotective action (Brzoska and others 2015b,2016b).

It is a well-known fact that polyphenols have a protective im-pact on the bones due to their antioxidative properties (Hubert andothers 2014). The worldwide literature delivers evidence that theconsumption of berries rich in polyphenols (plums, blueberries,blackberries, cranberries, black currants) is associated with reduc-ing the risk of age-related bone loss due to the antioxidative andanti-inflammatory action of these compounds exerted in the bonetissue (Hubert and others 2014). The results of our study suggestthat chokeberries may also be consumed for bone protection fromoxidative stress and oxidative damage (Brzoska and others 2016b).Moreover, our results allow to conclude that chokeberries mayprotect from the damaging action of other pro-oxidants on thebone.

Summarizing the findings of our study on the impact of aroniaberry extract on Cd turnover and toxicity, it can be hypothesizedthat A. melanocarpa berry products may be promising natural agentsfor the protection against Cd accumulation and skeleton damagein women chronically exposed to this heavy metal. According toour knowledge, our study is the first to investigate and reveal abeneficial impact of the consumption of chokeberry extract on themetabolism and biomechanical properties of the skeleton underboth physiological conditions and chronic exposure to osteotoxicheavy metal such as Cd.

The already published results of our own studies focused primar-ily on the investigation of the impact of chokeberry extract on thebody status of Cd and Cd-induced skeleton damage (Brzoska andothers 2013, 2015a, 2015b, 2016b; Roszczenko and others 2013);however, the possibility of protecting against other harmful effectsof the toxicity of this heavy metal is also a subject of our interest.Taking into account the above findings regarding the influence ofchokeberry extract on Cd accumulation in the liver and kidneys(Brzoska and others 2015a), it has been hypothesized by us thatthe consumption of the extract may also prevent liver and kidneydamage and the possible hepatoprotective impact is under investi-gation, whereas the influence on the kidneys will be investigatedin further studies. Our preliminary unpublished results show thatchokeberry extract may offer significant protection against Cd-induced liver damage and the findings will be published as soon aspossible.

It is important to underline that the protective impact offered bythe extract from A. melanocarpa berries observed in our experimen-tal model at Cd concentrations in the blood and urine, which arecomparable with the concentrations noticed in the general popu-lation, are very promising because they allow for the assumptionthat these effects may also occur in humans chronically exposedto this heavy metal. The possible prophylactic use of chokeberriesunder environmental exposure to Cd seems to be worthy of fur-ther investigation, involving epidemiological studies in both menand women.



Apart from the results obtained by Kowalczyk and others(2003b) and the above presented findings from our laboratory(Brzoska and others 2013, 2015a,b, 2016b; Roszczenko and others2013), there are no other data concerning the impact of choke-berry extract on Cd metabolism and toxic action under in vivoconditions. However, it is very important to underline that abeneficial impact of some compounds present in A. melanocarpaberries (including quercetin, chlorogenic acid, and p-coumaricacid) against Cd toxicity has also been revealed in vivo (Moralesand others 2006; Renugadevi and Prabu 2010; Krishnakumar andothers 2012; Wang and others 2013; Navaneethan and Rasool2014; Hao and others 2015). Quercetin (commercially availablepure compound) has been reported to protect from Cd-inducedhepatotoxicity (Vicente-Sanchez and others 2008; Prabu andothers 2011; Krishnakumar and others 2012) and nephrotoxic-ity (Morales and others 2006; Renugadevi and Prabu 2010; Wangand others 2013). Chlorogenic acid (commercially available purecompound) prevented brain damage caused by Cd (Hao and oth-ers 2015), whereas p-coumaric acid (commercially available purecompound) counteracted the nephrotoxic action of this heavymetal (Navaneethan and Rasool 2014). The protective impactof these polyphenolic compounds confirms the usefulness of A.melanocarpa berries in the protection from harmful effects of ex-posure to Cd.

The administration of quercetin (commercially available purecompound; 50 mg/kg b.w./24 h, 5 times a week for 4 wk, i.p.)increased the concentration of MT and the activity of endothe-lial NOS in the liver of rats exposed to CdCl2 (1.2 mg Cd/kgb.w./24 h, 5 times a week for 9 wk, subcutaneously – s.c.) anddecreased TBARS concentration in this organ (Vicente-Sanchezand others 2008). According to Prabu and others (2011), thepretreatment with quercetin (50 mg/kg b.w. for 28 d, per os– p.o.) decreased Cd-elevated (5 mg CdCl2/kg b.w. for 28 d,p.o.) activities of ALT, ALP, AST, lactate dehydrogenase (LDH),and gamma glutamyl transferase (GGTP), and concentrations ofbilirubin, TBARS, lipid hydroperoxides, and protein carbonyls inthe serum of rats. Quercetin also increased the concentrations ofreduced glutathione (GSH), total sulfhydryl groups (-SH), and vi-tamins C and E in the liver of the rats exposed to Cd as well as theactivities of antioxidative enzymes in this organ (Prabu and others2011). Moreover, quercetin administration (50 mg/kg b.w., p.o.)for 4 wk diminished Cd-increased (5 mg CdCl2/kg b.w. for 4 wk,p.o.) content of saturated lipids, collagen, and glycogen in hepato-cytes of rats (Krishnakumar and others 2012). This polyphenoliccompound also protected from changes in the structure of pro-teins (a decrease in the area of the amide I band and shifting ofthe position of this band to lower frequency values) and proteindenaturation (a significant increase in random coil and antiparallelβ-sheet structures and a decrease in α-helix and aggregated β-sheet structures) induced by Cd in the liver of rats (Krishnakumarand others 2012).

Renugadevi and Prabu (2010) have reported that quercetin(commercially available pure compound) prevented oxidativestress-related kidney dysfunction in rats exposed to Cd. The ad-ministration of this compound (7.5 mg/kg b.w. for 4 wk, p.o.)prior to exposure to CdCl2 (5 mg CdCl2/kg for 4 wk, p.o.) pre-vented Cd-induced histopathological changes in this organ (tubu-lar necrosis, thickening of basement membrane and luminal castformation), as well as biochemical alterations in the serum andurine reflecting the kidney status (increased concentrations of uricacid and creatinine in the serum, decreased concentrations of urea,uric acid, and creatinine in the urine, and decreased creatinine

clearance; Renugadevi and Prabu 2010). Moreover, the pretreat-ment with quercetin prevented Cd-induced increase in proteincarbonyl concentration, increased the concentrations of TBARSand lipid hydroperoxides, decreased the concentrations of total-SH groups, GSH, vitamin C and E, as well as decreased the ac-tivities of antioxidative enzymes (Renugadevi and Prabu 2010).Morales and others (2006) have noted that quercetin administra-tion (commercially available pure compound; 50 mg/kg b.w./day,5 times/week, i.p.) starting in the 4th week of the 9-wk exposureto Cd (1.2 mg Cd/kg b.w./day, 5 times per week, s.c.) decreasedthe plasma concentration of creatinine, urinary excretion of totalproteins, glucose, and enzymatic markers of renal tubular damage(N-acetyl-β-D-glucosaminidase, ALP, and GGTP) in rats. More-over, quercetin reduced the level of TBARS in the plasma andincreased the activities of SOD and GR in the kidneys of rats(Morales and others 2006). The protective influence of quercetin(commercially available pure compound) in regard to Cd-inducednephrotoxicity has been confirmed by the results of an in vitrostudy by Wang and others (2013) who have revealed that thispolyphenolic compound exerts cytoprotective effect on rat prox-imal tubular cells. P-coumaric acid (commercially available purecompound) has been reported to exert a protective impact on thekidneys by decreasing the Cd-induced concentrations of proin-flammatory cytokines (TNF-α and interleukin 1β) and increasingthe Cd-decreased activities of membrane-bound ATPases, elec-tron transport chain enzymes and glycolytic enzymes in the ratss.c. exposed to 3 mg CdCl2/kg b.w. (Navaneethan and Rasool2014). Moreover, Hao and others (2015) have revealed that i.g.administration of chlorogenic acid (commercially available purecompound) in a dose of 60 mg/kg b.w. for 30 d inhibited Cd-induced (5 mg CdCl2/kg b.w., p.o.) oxidative brain damage (re-flected in lipid peroxidation, depletion of antioxidants, reductionof membrane-bound ATPase activity, mitochondrial dysfunction,and DNA fragmentation) in mice.

Summarizing the above presented findings of experimentalstudies, it seems possible that chokeberry products may be use-ful in the protection against harmful effects of exposure to Cd,and epidemiological studies should be undertaken to confirm thepossible effectiveness of these products in humans.

PbApart from Cd, Pb is another toxic heavy metal hazardous to

the health of the general population, causing especially renal fail-ure (Rastogi 2008), hypertension (Vupputuri and others 2003),osteoporosis (Khalil and others 2014), and decreased hearing acu-ity (Choi and others 2012). Children are particularly susceptibleto the toxic action of this element. Even low exposure to Pb dur-ing early childhood may cause neuropsychological disorders anddeficits in intelligence quotient (IQ; Canfield and others 2003;Liu and others 2013). Intoxication with Pb via smoking and/orunder occupational conditions may be responsible for infertilityin men (Hsu and others 2009). Moreover, it has been suggestedthat exposure to this metal may contribute to the developmentof Alzheimer’s disease (Bakulski and others 2012). The generalpopulation is exposed to Pb mainly via food and drinking water(Echeverry and others 2015), and available data show that there isno safe level of environmental human exposure to this xenobiotic(Nawrot and Staessen 2006). Searching of means that may protectfrom exposure to this toxic metal is absolutely necessary.

The data on the effectiveness of the polyphenolic compoundsoccurring in aronia berries or their products in counteracting Pbtoxicity are very limited so far (Kowalczyk and others 2002, 2003a;



Liu and others 2010a). However, based on the available literatureit can be concluded that the consumption of aronia products mayprevent Pb-induced oxidative stress and its consequences, includ-ing oxidative damage to the liver (Kowalczyk and others 2002,2003a; Liu and others 2010a).

Kowalczyk and others (2002, 2003a) have revealed that a 3-mooral administration of the water extract of A. melanocarpa berriescontaining 100 mg of anthoyanins per liter to rats every other dayduring which lead acetate (Pb(CH3COO)2; at a concentrationof 400 mg/L) has not been given allowed to maintain, withinthe ranges of proper values, TBARS concentration in the serumand urine, and the concentrations of 8-OHdG and delta aminole-vulinic acid (δ-ALA) in the urine, while the exposure to Pb aloneincreased the values of these parameters. Moreover, the applicationof the extract to the rats chronically exposed to Pb(CH3COO)2decreased the concentrations of oxidized products of unsaturatedfatty acids in internal organs, bone tissue, and urine as well asthe protein carbonyls concentration in the serum (Kowalczyk andothers 2002, 2003a). Liu and others (2010a) have reported thatthe administration (by oral gavage) of quercetin (commerciallyavailable pure compound) in a daily dose of 10 mg/kg b.w. un-der a 10-wk exposure to 500 mg Pb/L in drinking water pro-tected from liver damage in rats. Quercetin normalized the oxida-tive/antioxidative balance and protected against the developmentof oxidative stress and its consequences in the liver of Pb-exposedrats. The administration of this polyphenolic compound underthe treatment with Pb maintained the activities of CAT, GPx,and SOD within the ranges of a control group as well as pre-vented Pb-caused increase in the levels of H2O2 and MDA inthe liver. Moreover, quercetin inhibited Pb-induced apoptosis bymodulating the ratio of apoptosis regulator protein (Bax) to B-celllymphoma 2 (Bcl-2) expression and suppressing the expressionof phosphorylated isoforms of N-terminal protein kinases (JNK1/2), and cleaved caspase-3 in this organ (Liu and others 2010a).As a result, quercetin entirely protected the liver from histologicalchanges (leukocyte infiltration and necrosis) caused by Pb.

Taking the above findings into account, it seems that A.melanocarpa berry products may play a role also in the protec-tion against harmful effects of exposure to Pb, but like in the caseof Cd, this issue needs further investigations.

EthanolThe consumption of alcoholic beverages is a very common cus-

tom all over the world (Ali and others 2011). Unfavorable healtheffects of excessive ethanol intake are well known and widely re-ported (Petti and others 2013; Ramamoorthi and others 2015).The main effects of toxic action of ethanol involve liver dam-age and depression of the central nervous system (Niedworok andothers 1997; Valcheva-Kuzmanova and others 2013b; Valcheva-Kuzmanova 2014). Moreover, ethanol abuse as well as chronicexposure to vapors of this substance will damage other organs andsystems (Molina and others 2003; Matsumoto and others 2004;Liu and others 2010b; Ramamoorthi and others 2015).

The available literature data from animal models show thatpolyphenolic compounds may be useful in the prevention andtreatment of the harmful health effects induced by ethanol (Nied-worok and others 1997; Molina and others 2003; Matsumotoand others 2004; Liu and others 2010b; Valcheva-Kuzmanovaand others 2013b; Valcheva-Kuzmanova 2014). On this basis andtaking into account the phenomenon known as “French paradox”(Lippi and others 2010), it may be supposed that polyphenoliccompounds can also exert a beneficial impact on subjects drinking

alcohol. The term “French paradox” describes a beneficial impactof the light consumption of red wine on human health. This phe-nomenon is attributed to the synergistic favorable action of smallor moderate amounts of ethanol (10 to 30 g per day which means1 or 2 glasses of wine) and polyphenolic compounds present inred wine, mainly resveratrol (Szmitko and Verna 2005; Lippi andothers 2010). Polyphenols and ethanol together may weaken ox-idative stress intensity and inhibit lipoprotein oxidation, enhancecholesterol efflux from vessel walls, and prevent macrophagecholesterol accumulation and foam-cell formation (Lippi andothers 2010) thus helping to prevent cardiovascular diseases andliver damage, which are the most common effects of excessiveethanol consumption.

The administration of A. melanocarpa berry products andpolyphenolic compounds present in chokeberries during and/orbefore ethanol consumption has also been observed to protectagainst the stomach damage and hepatotoxic and neurotoxic ac-tions of ethanol in animal models (Niedworok and others 1997;Molina and others 2003; Matsumoto and others 2004; Liu andothers 2010b; Valcheva-Kuzmanova and others 2013b; Valcheva-Kuzmanova 2014). Matsumoto and others (2004) have revealedwith a rat model that i.g. administration of A. melanocarpa crudeextract (at a dose of 2 g/kg b.w.) prevented gastric damage (ul-cerative changes and hemorrhage of gastric mucosa) induced byethanol when given at a dose of 10 mL/kg b.w. Anthocyanin dyeobtained from chokeberries (4 mg/kg b.w., p.o.) applied 2 h afterthe oral administration of 60% ethanol inhibited the xenobiotic-induced development of peptic ulcers and lipid peroxidation (ex-pressed as TBARS concentration) in the lungs, liver, and smallintestine of mice (Niedworok and others 1997). The pretreatmentwith chokeberry juice (in doses of 2,5, 5, and 10 mL/kg b.w.)exerted an antidepressive effect (increased locomotor activity andmitigated symptoms of anxiety and depression) in female Wistarrats treated with 8 g of ethanol/kg b.w. by oral gavage (1 h afterthe administration of this juice) for 14 d (Valcheva-Kuzmanovaand others 2013b; Valcheva-Kuzmanova 2014). The reduction ofalcohol-induced depressive effects is probably connected with theinfluence of polyphenolic compounds on the serotonergic and no-radrenergic neurotransmission because these compounds are ableto cross the blood–brain barrier and localize within the brain tissue(Machado and others 2008; Janle and others 2014; Kirakosyan andothers 2015). Liu and others (2010b) have reported that prein-cubation of rat hepatocytes with quercetin (at a concentration of50 µM) for 2 to 4 h protected against a decrease in the activityof SOD and the concentration of GSH, as well as an increase inMDA level and prevention of increased activities of the liver en-zymes (LDH and AST) induced by an 8-h hepatocyte incubationwith ethanol (at a concentration of 100 mM). Molina and others(2003) have also revealed that a 15-d pretreatment in mice withquercetin (25, 50, and 75 mg/kg b.w. by gastric intubation) priorto a 15-d dosage of 5 g ethanol/kg b.w. (by gastric intubation)protected the liver from xenobiotic-induced lipid peroxidation,increased the activities of SOD, CAT, GPx, and GR, and theconcentration of GSH as well as decreased the concentration ofoxidized glutathione (GSSG).

Although the possible protective impact of chokeberry productsin subjects drinking ethanol has not been investigated yet, theabove-mentioned data allow to hypothesize that the consumptionof these products, by individuals who drink alcoholic beverages,may have a protective and therapeutic impact and thus wide-designed epidemiological studies to investigate this hypothesis areneeded.



Carbon tetrachlorideThe constituents present in chokeberry juice have also been

noted to protect from the hepatotoxic action of another organicsolvent, namely CCl4 (Valcheva-Kuzmanova and others 2004).This compound, due to its chemical properties, is of grate use-fulness in the industrial sector and, thus, some individuals maybe chronically exposed to this compound (ATSDR 2005). A 2-dadministration of juice from chokeberries given by stomach in-tubation in doses of 5, 10, and 20 mL/kg b.w. after cessation ofexposure to CCl4 (0.2 mL/kg b.w. for 2 d, by stomach intubation)reduced necrotic and fatty changes in the rat liver, as well as inflam-matory infiltration of lymphocytes around the central vein, and itinhibited the activities of AST and ALT in the plasma (Valcheva-Kuzmanova and others 2004). Moreover, chokeberry juice de-creased a CCl4-induced increase in MDA concentration and pre-vented against GSH depletion in the liver (Valcheva-Kuzmanovaand others 2004).

Taking into account the findings by Valcheva-Kuzmanova andothers (2004), it seems possible that chokeberry juice and otheraronia berry products may be effective in the protection againstoxidative stress-related hepatotoxicity of other organochlorine hy-drocarbons, including chloroform; however, these effects have notbeen investigated yet.

N-nitroso compoundsN-nitroso compounds (N-nitrosoamines and N-nitrosoamides)

are formed during the storage of foodstuffs and in the stomach ofhumans and animals in the reaction of nucleophilic substitution be-tween nitrates(III) or nitrates(V) and amines (N-nitrosoamine for-mation) or amides (N-nitrosoamides formation; Dietrich and oth-ers 2005; Hmelak Gorenjak and Cencic 2013). The main sourcesof exposure to N-nitroso compounds are tobacco smoke (Schullerand Orloff 1998) and certain food products, especially smokedmeat and milk powder for infants (Dietrich and others 2005).Nitrates(III) and nitrates(V) are widely used in agriculture as fer-tilizers (Velthof and others 2014), while nitrates(III) are also usedas food preservatives. Thus, these N-nitroso compound precursorsare present in plant products, meat, and water (Hmelak Goren-jak and Cencic 2013). Nitrates(III) are also metabolites of somedrugs, especially nitroglycerine, isosorbide dinitrate and isosorbidemononitrate used for the treatment of angina pectoris (a painfulsymptom of ischemic heart disease; Fung 1983). Schuller andOrloff (1998) have revealed that nitrosamines present in tobaccosmoke constitute ligands for nicotinic acetylcholine receptors inhuman lung cancer cells.

N-nitrosoamines exert carcinogenic action in experimental an-imals (Mirvish 1995), and they have been recognized as potentialhuman carcinogens (Loh and others 2011). So far, there is no ev-idence that would allow to recognize if these compounds causecancer in humans; however, epidemiological studies have shownthe link between the presence of nitrates(III) and nitrates(V) in thediet and gastric cancers, as well as cancers of the urinary bladderand ovaries in inhabitants of industrialized countries (Weyer andothers 2001; Hernandez-Ramırez and others 2009).

Some experimental data suggest that the consumption of A.melanocarpa berries and their products may be useful in the pro-tection against hepatotoxicity of N-nitrosoamines (Kujawska andothers 2011) and their precursors (Atanasova-Goranova and oth-ers 1997). Kujawska and others (2011) have reported that a 28-dpretreatment with chokeberry juice (10 mL/kg b.w./24 h, p.o.)prevented oxidative changes in the liver (increased the concentra-tion of TBARS and oxidative DNA damage) of male Wistar rats

i.p. exposed to N-nitrosodiethylamine in a dose of 150 mg/kgb.w. Moreover, the pretreatment with chokeberry juice increasedthe activities of CAT, GPx, and GR, in comparison with the ratstreated with this compound alone (Kujawska and others 2011).

The possible protective impact of A. melanocarpa berries againstthe toxicity of N-nitroso compounds may be related to the antiox-idative properties of their ingredients, including especially antho-cyanins (Kujawska and others 2011), and to vitamin C (ascorbicacid; Leaf and others 1987; Tannenbaum 1989, Table 2). VitaminC is known to prevent formation of endogenous N-nitrosamines(Leaf and others 1987) and to reduce N-nitroso compounds to NOundergoing, during this redox reaction, transformation to dehy-droascorbic acid (Tannenbaum 1989). The ability of vitamin C todecrease the formation of N-nitrosoamines in the human body hasbeen confirmed in healthy subjects exposed to low concentrationsof N-nitrosoproline precursors. The administration of vitamin Cdecreased N-nitrosoproline concentration in the urine (Tannen-baum 1989). Indeed, Atanasova-Goranova and others (1997) haverevealed that A. melanocarpa nectar (1 mL/100 g b.w.) given for3 consecutive days by oral intubation during the exposure toaminopyrin (12.5 mg/mL) and sodium nitrate(III) (11 mg/mL)for 3 d prevented endogenous N-nitrosamine formation in theliver of rats. At the same time, the administration of the nectar hadbeneficial impact on the liver, as reflected in decreased concen-trations of hepatotoxicity markers (glutamic-oxaloacetic transam-inase, glutamic-pyruvic transaminase, and uric acid) in the serumand lipid concentration in hepatocytes as well as in complete pre-vention of dystrophic changes in the liver (centrolobular necrosis,enlarged cells with 2 large pyknotic nuclei, and intense exangia;Atanasova-Goranova and others 1997). Some polyphenolic com-pounds (such as cinnamic acid and secoisolariciresinol) have beenreported (Hernandez-Ramırez and others 2009) to prevent N-nitrosoamine formation in the stomach; however, the possibilityof such action of polyphenolic compounds present in chokeberrieshas not been studied yet.

ParaquatAmong toxic substances which constitute danger to human

health attention should also be paid to pesticides, which are aclass of biocides commonly used for the protection from pests,including vectors of human or animal diseases as well as unwantedspecies of plants and animals (Magner and others 2015). The gen-eral population of industrialized countries is exposed to pesticideresidues mainly through the diet (Melnyk and others 2014). More-over, accidental poisonings caused by these toxic compounds oc-cur among children and farmers (Peiro and others 2007; Chenand others 2010).

In the available literature there is no information about theprotective role of chokeberries and products made from themregarding human exposure to pesticides. However, some data ob-tained with animals and in in vitro models indicate that polypheno-lic compounds present in chokeberries, such as chlorogenic acid,quercetin, and kaempferol, may protect from oxidative damage in-duced by paraquat (N,N′-dimethyl-4,4′-bipyridinium dichloride),which is a widely used herbicide (Tsuchiya and others 1996; Parkand others 2010; Podder and others 2014). This compound ischaracterized by high toxicity to humans and animals related to itsredox activity (Dou and others 2016). Exposure to this xenobioticleads to liver (Peiro and others 2007) and lung damage (Chen andothers 2010). Moreover, this compound has been recognized tocontribute to the development of Parkinson’s disease (Chen andothers 2012). The accidental intake of paraquat by children may



cause death due to respiratory failure (Chen and others 2010).This pesticide may be absorbed into the organism even throughhuman skin contact (Peiro and others 2007).

The 1st suggestion on the protective action of polyphenolspresent in chokeberries against paraquat toxicity was made byTsuchiya and others (1996) who revealed that supplementationwith 2 mg of chlorogenic acid (isolated from unroasted coffeebeans) per g of diet for 10 d normalized the activity of GPx in theliver and erythrocytes, as well as the liver activities of CAT and GRin rats after consumption for 10 d of the diet containing 0.2 mg ofparaquat/g. Moreover, chlorogenic acid prevented the paraquat-induced decrease in food intake and b.w. gain of rats (Tsuchiya andothers 1996). Park and others (2010) have reported that quercetin(commercially available pure compound) given twice at a dose of50 mg/kg b.w. (i.p.) 2 and 6 h after i.p. paraquat application (50mg/kg b.w.), and administered for 14 d (50 mg/kg b.w., i.p.) aftera single dose of paraquat (0.5 mg/kg b.w. directly into the rightlung), protected from this pesticide-induced lipid peroxidation, anincrease in MDA concentration, and a decrease in GSH concen-tration in the lung of rats. The study by Podder and others (2014)confirms the possibility of protective impact of A. melanocarpaberries on the lungs after exposure to paraquat. These authorshave found that kaempferol protects human bronchial epithelialBEAS-2B cells from oxidative stress induced by this pesticide.

In the available literature we have found no other investigationson the impact of A. melanocarpa berry products, or the aronia fruit-occurring polyphenols, on the effects of toxic action of otherpesticides. However, it seems highly probable that aronia berryproducts may also be effective at least against one other herbicide –diquat, which also exerts its toxic action via free radical mechanism(Jones and Vale 2000). Further research on this matter is necessary.

Polyaromatic hydrocarbons (PAH)PAH have been classified by the International Agency for Re-

search on Cancer as human carcinogens (ATSDR 2009). Peopleare exposed to these compounds mainly through food products(especially smoked, fried, baked, and grilled products), air, andwater, as well as through tobacco smoke (Gasiorowski and others1997; Szaefer and others 2011; Rengarajan and others 2015).

The beneficial influence of chokeberries relative to the mainPAH occurring in tobacco smoke, such as benzo-[a]-pyrene and7,12-dimethylbenz[a]anthracene, has been published (Gasiorowskiand others 1997; Szaefer and others 2011). Szaefer and others(2011) have reported that the pretreatment of rats with choke-berry juice (8 mL/kg b.w. for 28 d by gastric gavage) decreasedthe concentrations of bilirubin, creatinine, and urea nitrogen inthe blood, as well as the activities of AST, sorbitol dehydroge-nase, and GGTP in the serum elevated by i.p. administration of7,12-dimethylbenz[a]anthracene at a dose of 10 mg/kg b.w. for2 d. Moreover, the pretreatment with this juice changed the ac-tivity of 2 isoforms of cytochrome P-450, such as CYP1A1 andCYP2B, involved in the activation and detoxification of 7,12-dimethylbenz[a]anthracene, respectively. The activity of CYP1A1was reduced, while that of CYP2B was increased due to the ad-ministration of chokeberry juice resulting in an enhanced detox-ification of 7,12-dimethylbenz[a]anthracene (Szaefer and others2011). Moreover, Gasiorowski and others (1997) revealed an an-timutagenic activity of the anthocyanin fraction from chokeber-ries against benzo-[a]-pyrene using the in vitro Ames test. Theauthors also noted a decrease in the frequency of sister chromatidexchange induced by benzo-[a]-pyrene in the Sister ChromatidExchanges (SCEs) test with human blood-derived lymphocytes

culture. Moreover, anthocyanins from chokeberries markedly in-hibited the generation and release of superoxide radicals by humangranulocytes exposed to benzo-[a]-pyrene in an in vitro model(Gasiorowski and others 1997).

It has been estimated that the administration of 8 mL chokeberryjuice per kg of b.w. to rats (about 300 g each) corresponds to anaverage daily consumption by humans (weighing 70 kg each) of500 to 600 mL of juice (Szaefer and others 2011). On this basis,and taking into account the findings by Szaefer and others (2011),it can be supposed that the daily consumption of half a liter or alittle more of chokeberry juice for at least a month can protectfrom hepatotoxic action of PAH in human. Further studies areneeded to confirm the possible effectiveness of A. melanocarpaberry products to protect from the harmful effects of exposure toPAH.

Sulfur mustard and its derivativesSulfur mustard (yperite, bis(2-chloroethyl)sulfide) is a chemical

warfare agent which causes serious blisters and chemical burnswhen in contact with the skin (Gautam and others 2007). Thistoxic gas and its derivatives have been reported to induce oxidativestress in red blood cells, skin, lungs, liver, spleen, and the smallintestine of humans (Ghanei and Harandi 2010) or experimentalanimals (Kumar and others 2001; Kowalczyk and others 2004;Gautam and others 2007). Mutagenic and carcinogenic effects(lung cancer) after accidental exposure to sulfur mustard gas havebeen reported for soldiers and civilians (Ghanei and Harandi 2010).

In the available literature, we can find experimental data in-dicating that anthocyanins from chokeberries may provide pro-tection against the toxicity of yperite and its derivative – sulfide2-chloroethyl-3-chloropropyl (Kowalczyk and others 2004; Gau-tam and other 2007). An aqueous solution of anthocyanins fromA. melanocarpa berries (given only once at a dose of 1.0 mg/kg b.w.by a stomach tube) together with the toxic sulfide 2-chloroethyl-3-chloropropyl (54 mg/kg b.w. by a stomach tube) completelyprevented (24 h after intoxication) the compound-induced de-crease in CAT activity in the red blood cells, as well as partiallyprotected against lipid peroxidation in the lungs and small intes-tine (decreased the concentration of TBARS compared to thegroup treated with this sulfur mustard derivative alone; Kowal-czyk and others 2004). The pretreatment with quercetin (in dosesof 100 and 200 mg/kg, i.p.) 30 min before exposure to sulfurmustard (19.3 mg/kg b.w., percutaneously) decreased the concen-tration of MDA and increased the concentration of GSH in theliver, spleen, and skin of mice, compared to the group exposedonly to sulfur mustard. Moreover, quercetin protected the nor-mal histology of the spleen (reduced congestion and parenchymalatrophy induced by yperite), diminished histological changes inthe liver (necrosis, proliferation of bile duct parenchyma, hepaticvacuolation, hemorrhage, infiltration, clumping of cytoplasm, andobliteration of chromatin), as well as mitigated lesions in the skin(dermo-epidermal separation, invasion of the epidermis by acuteinflammatory cells, and accumulation of exudates composed offibrinoid material and red blood cells; Gautam and others 2007).

MethamphetamineNowadays, the addiction to psychoactive substances is a grow-

ing problem all over the world (Valenca and others 2013). One ofthe most popular and, at the same time, one of the most dangerousnarcotics is methamphetamine. This substance is a highly addic-tive drug acting as a stimulant for the central nervous system.Methamphetamine causes cardiac dysrhythmias, hypertension,



hallucinations, violent behavior, and dental problems (“methmouth,” rampant carries, excessive tooth wear; Naidoo and Smit2011; Rusyniak 2013). Chronic methamphetamine abuse is de-structive to the central nervous system. It leads to psychosis, deficitsin memory, anxiety, and depression (Rusyniak 2013). Thus, spe-cial attention should be focused on looking for effective ways ofcounteracting the unfavorable health effects of taking metham-phetamine and its treatment.

In the available literature we have found only one report, byKoriem and Soliman (2014), which revealed that chlorogenic acidbelonging to the main polyphenolic compounds present in choke-berries may be useful for the partial prevention of hepatotoxicityand brain damage induced by methamphetamine. The authorshave noted that a 1-d pretreatment with chlorogenic acid (com-mercially available pure compound; 60 mg/kg b.w., i.p.) of ratsexposed to methamphetamine (10 mg/kg b.w. twice daily for7 d, i.p.) entirely prevented methamphetamine-induced increasein the serum activities of the liver marker enzymes (AST, ALT, andALP) and the concentrations of bilirubin, triglycerides, and LDL,as well as lipid peroxidation (expressed as MDA concentration) inthe serum, liver and brain. Furthermore, the prior administrationof chlorogenic acid protected from methamphetamine-caused in-crease in the liver concentration of NO and changes in the serumconcentrations of total protein, albumin, globulin, and the ratio ofalbumin and globulin concentrations. Moreover, chlorogenic acidnormalized the brain concentrations of neurotransmitters such asserotonin, norepinephrine, and dopamine, as well as the activitiesof SOD and GPx in the blood and liver (Koriem and Soliman2014).

Unfortunately, according to our knowledge, the possibility ofusing extracts and other products from A. melanocarpa berries forcounteracting the effects of methamphetamine or any other nar-cotic taken by both humans and experimental animals has notbeen investigated yet. However, the data on the effectiveness ofchlorogenic acid in the prevention of hepatotoxicity and braindamage caused by methamphetamine (Koriem and Soliman 2014)allow to suppose that aronia fruit products may offer protection toindividuals taking drugs or being addicted to them. Further studiesare needed on this matter.

Tobacco smoke and its componentsApart from excessive ethanol consumption and drug abuse ha-

bitual tobacco smoking is an important public health problem(Abdou and Elsaerei 2004; Talio and others 2010; Leung andothers 2013; Petti and others 2013; Gonzalez-Suarez and others2014). The harmful effects of tobacco smoke caused by its verynumerous chemical components (Abdou and Elsaerei 2004; Talioand others 2010; Leung and others 2013; Gonzalez-Suarez andothers 2014), including mutagenic and carcinogenic agents thatnow are well known and widely reported (Abdou and Elsaerei2004; Talio and others 2010; Leung and others 2013). Tobaccosmoke is the main nonoccupational source of human exposure tomutagens and carcinogens (Abdou and Elsaerei 2004; Talio andothers 2010; Leung and others 2013).

Balansky and others (2012) have reported a beneficial effectof chokeberries in an experimental model with mice reflectingthe situation of the consumption of an aqueous black chokeberryextract 6 times daily by humans after cigarette smoking. The ad-ministration of a 17.5% extract of black chokeberry for 8 moduring and after the exposure to cigarette smoke (6 times dailyfor 10 min by drawing 15 consecutive puffs, for 4 mo) preventedhistopathological alterations in the lungs (emphysema, blood vessel

proliferation, alveolar epithelial hyperplasia, and lung adenomas),liver degeneration, and damage to the circulating erythrocytes, aswell as prevented weight loss in mice (Balansky and others 2012).Khandelwal and Abraham (2014) have revealed that cyanidin andpelargonidin used alone protected from DNA damage in the bonemarrow of mice treated with diepoxybutane and urethane whichare found in cigarette smoke.

A strong argument for the effectiveness of the products madefrom chekoberries in counteracting the harmful effects of tobaccosmoke is revealing the potential of some ingredients of A.melanocarpa berries to protect from the effects of toxic actionof various tobacco smoke components (Gasiorowski and others1997; Kowalczyk and others 2002, 2003a; Kujawska and others2011; Szaefer and others 2011; Brzoska and others 2013, 2015a,2015b, 2016b; Roszczenko and others 2013). The protectiveimpact of chokeberry-made products and some polyphenoliccompounds occurring in them, regarding such components oftobacco smoke such as heavy metals, PAH, and N-nitroso com-pounds, was presented and discussed in previous subsections of thisreview. Moreover, the beneficial influence of another componentof tobacco smoke – 2-amino fluorine, belonging to polyaromaticamines (Gasiorowski and others 1997), has been reported.Gasiorowski and others (1997) have revealed an antimutagenicactivity of the anthocyanin fraction from chokeberries against2-amino fluorine in the in vitro Ames test. They have also notedthat anthocyanins from chokeberries markedly inhibited the gen-eration and release of superoxide radicals by human granulocytesexposed to 2-amino fluorine in an in vitro model (Gasiorowski andothers 1997).

Many harmful chemicals present in tobacco smoke are capa-ble of acting via oxidative stress (Varela-Carver and others 2010)and the beneficial impact of aronia berries regarding the effectsof cigarette smoking may be, at least to some extent, a result ofthe antioxidative properties of polyphenolic compounds, vitamins,and minerals present in these berries. The above presented litera-ture data on the beneficial impact of aronia extract and its variousingredients regarding unfavorable effects caused by tobacco smokeor its components are particularly promising because they sug-gest the possibility of prophylactic use of chokeberries and theirproducts by habitual tobacco smokers.

MedicinesDue to the increasing incidence of numerous diseases, including

cancers (Wolk and others 2014; Siegel and others 2015), a part ofthe general population takes medications repeatedly for long peri-ods of time. Many such drugs, especially anticarcinogenic agents,even at therapeutic doses, cause side effects. Research performedin laboratory animals and with in vitro models indicates that ex-tracts and juice from A. melanocarpa berries may protect from toxiceffects connected with pro-oxidative and pro-inflammatory prop-erties of some drugs, including amiodarone (an antiarrhythmiccausing pneumotoxicity; Valcheva-Kuzmanova and others 2014),indomethacin (a nonsteroidal anti-inflammatory drug; Valcheva-Kuzmanova and others 2005), cisplatin (a cytotoxic chemotherapydrug; Valcheva-Kuzmanova and others 2013a), cyclophosphamide(an anticancer alkylating drug; Niedworok and others 1995), andziprasidone (an antipsychotic drug used in patients suffering fromschizophrenia; Dietrich-Muszalska and others 2014). Moreover,quercetin (commercially available pure compound) has been re-ported to prevent some side effects of paracetamol (an over-the-counter analgesic and antipyretic drug; El-Shafey and others 2015),isoniazid (an antibiotic used as a 1st-line agent in the prevention



and treatment of tuberculosis; Qader and others 2014), rifampicin(an antibiotic used in the treatment of tuberculosis, influenza,and meningococcal disease; Qader and others 2014), etoposide (a1st-line anticancer drug used in the treatment of tumors, lym-phomas, and leukemias; Papiez and Krzysciak 2014), triptolide(a diterpene triepoxide with anti-inflammatory, anticancerogenic,immunomodulatory, and proapoptotic activities obtained from themedicinal plant Triterygium wilfordii; Hu and others 2015), and cis-platin (Kuhlmann and others 1998).

Dietrich-Muszalska and others (2014) have reported that a 24-h incubation of the plasma obtained from healthy subjects withziprasidone (at concentrations of 40, 139, and 250 ng/mL) andAronox (at a concentration of 50 µg/mL) resulted in a signifi-cant weakening of the intensity of lipid peroxidation (evaluatedbased on TBARS concentration) compared to the plasma incu-bated with ziprasidone alone. According to Niedworok and others(1995), anthocyanins present in chokeberry extract (administeredat a dose of 1 mL/kg b.w. for 7 d) are capable of protecting from ox-idative stress in the blood of rabbits induced by cyclophosphamide(administered i.v. at a dose of 6 mg/kg b.w. for 3 d). More-over, A. melanocarpa fruit juice (at concentrations of 0.05 mg/mLand 0.1 mg/mL) protected from cisplatin-induced cytotoxicityin the human embryonic kidney cell line HEK293T (Valcheva-Kuzmanova and others 2013a). A. melanocarpa fruit juice (givenorally at doses of 5 and 10 mL/kg b.w. for 10 d) prevented lipidperoxidation (expressed as the level of MDA) and fibrosis of thelungs (assessed based on the level of hydroxyproline) induced byamiodarone (given intratracheally for 2 d at a dose of 6.25 mg/kgb.w.; Valcheva-Kuzmanova and others 2014). Chokeberry juice (5,10, and 20 mL/kg b.w. administered p.o. 1 h before indomethacindosage) decreased the concentrations of MDA and GSSG, di-minished the number and area of indomethacin-induced gastriculcers, increased the production of gastric mucus, as well as in-creased GSH concentration in the stomach of rats s.c. treated withindomethacin at a dose of 30 mg/kg b.w. (Valcheva-Kuzmanovaand others 2005).

Quercetin (commercially available pure compound) has alsobeen reported to protect against oxidative damage induced bysome medications in the liver and kidney (Kuhlmann and others1998; Papiez and Krzysciak 2014; El-Shafey and others 2015; Huand others 2015). El-Shafey and others (2015) have revealed thatpretreatment with quercetin (15 mg/kg b.w./24 h for 21 con-secutive days, p.o.) markedly decreased the paracetamol-increased(given in a single oral dose of 3 g/kg b.w.) levels of markers of hep-atotoxicity (ALT, AST, ASP, and GGTP) and nephrotoxicity (totalprotein, urea, and creatinine) in the serum, as well as the levelsof markers of oxidative stress consequences (TBARS and proteincarbonyls) in the liver, and kidneys, and NO concentration in theserum, liver and kidney of rats. Moreover, quercetin increased themitochondrial production of energy via inhibiting the reductionof the content of adenosine triphosphate in the liver and kid-ney caused by paracetamol (El-Shafey and others 2015). Qaderand others (2014) have reported that quercetin dosage (commer-cially available pure compound; 300 mg/kg b.w., p.o.) for 42 dprior to the daily administration of 10 mg isoniazid per kg b.w.(p.o.), together with 10 mg of rifampicin per kg b.w. (p.o.) for42 d, prevented the isoniazid- and rifampicin-induced increasein the activities of AST and ALT in the liver, increased the liverantioxidative potential, and improved the histopathological struc-ture of this organ (decreased eosinophils infiltration in the portaltract and Kupfer cell hyperplasia; Qader and others 2014). Fur-thermore, quercetin (commercially available pure compound) has

been noted to protect from oxidative stress induced by etopo-side in leukemic promyelocytic HL-60 cells (Papiez and Krzysciak2014), triptolide in rat Leydig cells (Hu and others 2015), and cis-platin in renal tubular epithelial cells (Kuhlmann and others 1998).It has been revealed that quercetin (0.5 to 100 µM) incubatedwith etoposide (1 to 10 µM) and human promyelocytic leukemiacells (HL-60 cells) for 1 h decreased ROS formation in thesecells (Papiez and Krzysciak 2014). Moreover, the incubation ofquercetin (0.5 to 1 µM) with HL-60 cells and etoposide (10 µM)for 24 h decreased the concentration of the late apoptotic cells thatare increased by etoposide (Papiez and Krzysciak 2014). On thisbasis, it may be concluded that quercetin should not be used in thecase of human promyelocytic leukemia because this polyphenoliccompound can diminish the effectiveness of therapy with etopo-side. But further research on this matter is necessary.

Based on the available data, it seems that the above-describedbeneficial impact of aronia berry products and quercetin againstthe side effects induced by some medications is connected with theantioxidative properties of chokeberry ingredients. Thus, it seemspossible that polyphenols from chokeberries may also be usefulin the prevention of side effects caused by other medications thatinduce oxidative stress. Side effects of some therapies, includingmainly treatment with cytotoxic anticancer drugs constitute animportant medical problem. Thus, the attention of medical practi-tioners, including oncologists, should be focused on the possibilityof using aronia berry products to counteract negative effects oc-curring under the application of anticancer medications. It seemsvery interesting to investigate whether the consumption of aronia-made products by subjects undergoing anticancer therapies couldhave a protective impact.

The Safety of Using Chokeberries and their ProductsThe consumption of A. melanocarpa berries and products made

from them is broadly recommended; however, until now an effec-tive and safe quantity of these products has not been established andfurther studies to recognize doses which have a beneficial impacton human health, useful in counteracting various abnormalities,are necessary. Currently, there is no evidence of any unwantedand toxic effects of A. melanocarpa berries and products made fromthem in both human and experimental animals.

On the other hand, the results of some studies performed in an-imal models suggest that some compounds present in chokeberriesare harmful to health when they are consumed at extremely highdoses (Hagiwara and others 1991; Dunnick and Hailey 1992).Hagiwara and others (1991) have revealed that the consumptionof caffeic acid at a dose of 2000 mg/kg diet for 104 wk in ratsand for 96 wk in mice resulted in forestomach squamous cell pa-pilloma or carcinoma, as well as in renal tubular cell hyperplasiaand adenoma, in both sexes of these animals, and alveolar type IIcell tumors in male mice. Dunnick and Hailey (1992) have re-ported that a high dose of quercetin (approximately 1900 mg/kgb.w./24 h) delivered in a diet for 2 y caused chronic nephropathyin rats (neoplastic lesions in kidneys, hyperplasia, and neoplasiaof the renal tubular epithelium). However, it is important to un-derline that such a high intake of polyphenolic compounds withthe standard diet and aronia berry products is almost impossiblein humans. It has been evaluated that the average man (weighing70 kg) would have to drink at least 2 L of aronia juice every dayfor 2 y to consume similar amounts of quercetin (in calculationper b.w.) to those which led to nephropathy in rats (Dunnick andHailey 1992). But, it should also be considered, that owing tothe ability of polyphenols to form stable complexes with divalent



and trivalent metals, including bioelements (Liu and Guo 2015),the prolonged excessive consumption of products rich in thesecompounds may result in essential metal deficiencies in the body(Zijp and others 2000). Thus, nutritionists should recommend therational use of aronia polyphenol-based dietary supplements.

It is also important to emphasize that none of the chokeberryproducts should be consumed immediately after swallowing drugsand together to avoid interactions between active drug compo-nents and compounds present in these products. Procyanidins (es-pecially procyanidin B5) and anthocyanins (mainly cyanidin 3-arabinoside) present in chokeberries are inhibitors of CYP3A4, anenzyme responsible for the biotransformation of drugs, so some ofthem (such as midazolam) should not be drunk with chokeberryjuice due to their slower biotransformation which might cause anintensification of their action (Braunlich and others 2013a).

Taking into account the available literature data, it seems safe tosay that there is no risk of an overdose of polyphenols providedthat the products and dietary supplements containing chokeberriesare used rationally. Moreover, the positive impact of a regularconsumption of chokeberry products on human health withoutany side effects, which has been noticed in many studies (Simeonovand others 2002; Skoczynska and others 2007; Kardum and others2015), confirms the safety of using of aronia berries in both healthysubjects and those affected by various diseases.

Although consumption of A. melanocarpa berries and productsmade of them is beneficial and rather safe for human health, forma-tion of stable complexes of polyphenolic compounds with bioele-ments, including among others zinc, copper, and iron, during theprolonged enhanced consumption of chokeberry products cannotbe excluded and may result in essential metal deficiencies in thebody (Zijp and others 2000; Liu and Guo 2015). This issue isnowadays studied by us.

Concluding RemarksA. melanocarpa berries are one of the richest sources of polyphe-

nols available. Numerous and indisputable studies that chokeber-ries can be effective in the prevention and treatment of some dis-eases, including noncommunicable diseases, have been provided.The available data suggest that A. melanocarpa berries and productsmade from them, mainly due to the high content of polyphenoliccompounds possessing antioxidative, anti-inflammatory, and an-tibacterial properties, may be useful dietary supplements for theprevention and treatment of noncommunicable diseases, especiallycardiovascular system disorders, diabetes, and digestive system dis-orders. Moreover, the data obtained from various in vitro modelssuggest that a long-term regular consumption of chokeberry prod-ucts and extracts obtained from A. melanocarpa leaves may preventsome types of cancers, but these results need confirmation fromin vivo models. It is also possible that chokeberries and productsmade from them may be useful for the treatment of skin disorders,the common cold, and reproductive system and nervous systemdisorders, as well as for the improvement of eyesight. Chokeberriesand products made from them are recommended to be consumedwith a daily diet similar to green tea whose beneficial impact (con-nected with the presence of polyphenolic compounds) on health isno widely known. The available data suggest that the consumptionof at least 1 glass (200 to 250 mL) of chokeberry juice for a fewmonths may be useful for the prevention of the development ofvarious noncommunicable diseases, especially cardiovascular sys-tem disorders and diabetes. Due to the fact that chokeberries arevery rich in anthocyanins, it is supposed that they can be recom-mended in dietary supplements for the improvement of vision.

Moreover, attention should be paid to the possibility of usingchokeberries and aronia leaves as raw materials, rich in polyphe-nolic compounds, for the production of cosmetics.

It is important to underline that the results of experimentalstudies, performed with animal models, and in in vitro modelssuggest a role of A. melanocarpa berries and their products, andsingle polyphenolic compounds present in them, for the preven-tion and treatment of health disorders caused by exposure to someof the toxic substances present in air, water, and food, includ-ing those recognized to be particularly harmful, such as tobaccosmoke and its components, ethanol, methamphetamine, and cer-tain medicines. Thus, attention of scientists should be paid tothe possibility of using products made from chokeberries for theuse of people exposed to toxic substances environmentally and atthe workplace, especially to substances inducing oxidative stress,such as heavy metals which may be complexed by polyphenoliccompounds. Although all the data in this regard come from ex-perimental in vivo and in vitro studies, and there is no evidenceof the effectiveness of A. melanocarpa products against xenobioticsin humans, the available results of experimental studies are verypromising for humans.

It is important to underline that all studies aimed to evaluatethe role of products made from A. melanocarpa berries and aroniaproducts with polyphenolic compounds for the prevention andtreatment of noncommunicable diseases, as well as in the coun-teraction of unfavorable effects of toxic xenobiotics have revealedeffectiveness.

Summarizing, more attention should be focused on the useful-ness of A. melanocarpa for the protection and treatment of noncom-municable diseases and possible effectiveness in counteracting theunfavorable effects of exposure to xenobiotics. The presented anddiscussed literature data, including our own experimental findings,on the protective impact of A. melanocarpa products, and somepolyphenolic compounds present in the aronia berries or leaves,regarding various unfavorable effects of toxic action of xenobi-otics, are very promising and allow to hypothesize that chokeber-ries and their products may be effective preventive and therapeuticagents for humans exposed to numerous xenobiotics. Thus, fur-ther studies, including epidemiological investigations are necessaryto confirm the effectiveness of A. melanocarpa, and to explain thepossible mechanisms of the beneficial action of its ingredients, andto establish the recommended intake of aronia berry products.

AbbreviationsALP alkaline phosphataseALT alanine aminotransaminaseA. melanocarpa Aronia melanocarpaAST aspartate aminotransferaseBMI body mass indexb.w. body weightCAT catalaseCCl4 carbon tetrachlorideCd cadmiumCdCl2 cadmium chlorided.w. dry weightGGTP gamma glutamyl transferaseGPx glutathione peroxidaseGR glutathione reductaseGSH reduced glutathioneGSSG oxidized glutathionef.w. fresh weightHbA1c glycated hemoglobin



HDL high-density lipoproteinHepG2 human liver cell lineHL60/DOX human promyelocytic leukemia cells resistant

to doxorubicinHL60/VINC human promyelocytic leukemia cells resistant

to vincristineH2O2 hydrogen peroxideIC50 half maximal inhibitory concentrationi.g. intragastricalIL-6 interleukin-6IL-8 interleukin-8i.p. intraperitoneally (intraperitoneal)IQ intelligence quotientLDH lactate dehydrogenaseLDL low-density lipoproteinMDA malondialdehydeMT metallothioneinNAFLD non-alcoholic fatty liver diseaseNF-κB nuclear factor kappa-light-chain-enhancer

of activated B cellsNO nitric oxideNOS nitric oxide synthaseOH hydroxyl groupox-LDL oxidized form of low-density lipoproteinPAH polycyclic aromatic hydrocarbonsPb leadPb(CH3COO)2 lead acetatePGE2 prostaglandin E2p.o. per osROS reactive oxygen speciess.c. subcutaneously (subcutaneous)-SH sulfhydryl groupSOD superoxide dismutaseTBARS thiobarbituric acid-reactive substancesTNF-α tumor necrosis factor alphaTAS total antioxidative statusTOS total oxidative statusUVB radiation ultraviolet B radiationVCAM-1 vascular cell adhesion molecule 1WHO World Health Oganization8-OHdG 8-hydroxy-2’-deoxyguanosine

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