Biomed Res International Gymnema

8/10/2019 Biomed Res International Gymnema

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BioMed Research International

Te present review is a research update on Gymnema syl-vestre, a rare herb with signi cant medicinal attributes withan overview o its ethnobotanical uses, phytochemistry deal-ing with an in-depth study o its phytochemicals, and theirbioactivities. It also explores the acts and prospects o itsdevelopment into a modern and efficient therapeutic, con-

temporary with thepresent trendso pharmacology anddrugdevelopment. Furthermore, it holds signi cant prospects inmajor health problems like cardiovascular disorders, obesity,osteoporosis, andasthma besides being a popular medication

or number o other health ailments. Te herb nds signi -cant application in various ood preparations or control o obesity and blood cholesterol levels besides regulation o sugar homeostasis. Te herbal preparations o G. sylvestrearepresently used in tea bags, health tablets and supplements,beverages, and con ectioneries.

2. Traditional Perspective

G. sylvestreis an indigenous herb,belongingto theclassdicot-yledonous o the amily Asclepiadaceae. Te plant is a goodsource o a large number o bioactive substances [ ]. It hasdeep roots in history, being one o the major botanicals usedin Ayurvedic system o medicine to treat conditions ranging

rom diabetes, malaria, to snakebites [ ]. Te herb is cultiv-ated worldwideandalso known as Chigengteng or AustralianCowplant, Waldschlinge in German, periploca o thewoods inEnglish and gurmar in Hindi [ ].

3. Taxonomy

G. sylvestre R.Br. is a perennial, woody climber belonging toamily Asclepiadaceae or the milk weed amily []. Te

genus is classi ed into species, some o which like G. syl-vestre, G. montanum , G. yunnanense, and G. inodorum havemedicinal properties [ ]. Te plant is ound in tropicaland subtropical regions, well distributed in parts o centraland southern India and in the southern part o China, trop-ical A rica, Malaysia, and Sri Lanka []. G. sylvestre is slow growing herb, ound ideally in tropical andsubtropical humidclimate and common in hills o evergreen orests. It is a clim-ber and generally requires support or growth. Te seeds aresown in the months o November-December and harvested

rom September to February. Te propagation through seedgermination is difficult due to lowviabilityo theseeds; there-

ore,the alternativehasbeen root cuttingswhich are generally planted in the monthso June and July [ ]. erminalcuttingswith three o our nodes have also been used as or vegetativepropagation and usually planted in the month o February-March [ ]. Te leaves are opposite, usually elliptic or ovate( . . inch . . inch), in orescence is lateral umbelin cymes; ollicles are terete and lanceolate, up to inches inheight. Corolla is pale yellow in colour, valvate, campanulatewith single corona with eshy scales. Te calyx-lobes arelong, ovate, obtuse, and pubescent. Carpels- , unilocular,ovules locules may be present, anther connective producedinto a membranous tip [ , ].

4. Phytochemical Profiling

Te leaves o G. sylvestre contain triterpene saponins belong-ing to oleanane and dammarane classes. Te major constitu-ents like gymnemic acids and gymnemasaponins are mem-bers o oleanane type o saponins while gymnemasides aredammarane saponins [ , ]. Other phytoconstituents in-clude anthraquinones, avones, hentriacontane, pentatria-contane,phytin, resins, tartaric acid, ormic acid,butyricacid,lupeol, -amyrin related glycosides, stigmasterol, and cal-cium oxalate [ ]. Te presenceo alkaloidshadbeen detectedin plant extracts. Leaves o G. sylvestre have acidic glycosidesandanthraquinones and theirderivatives [ ]. Temajor sec-ondary metabolites in Gymnema includes a group o nineclosely related acidic glycosides, the main are gymnemic acidAD and ound in all parts o the plant (see Supplementary

able in supplementary materials available online at http://dx.doi.org/ . / / ). Te maximum content o gymnemicacidis ound in shoottips( . mg-g1 DW) andleast in seeds ( . mg-g1 DW). Antisaccharin property o gymnemicacidA 1 wasgreatly reduced onconversion into A 2 ,while no activity was observed in case o A3 suggesting thatthe ester group in the genin portion o gymnemic acid im-parts the antisweet property to the triterpene saponins, thegymnemic acids. Gymnemic acids A 2 and A3 possessed bothglucuronic acid and galactose in their molecular structureswhile glucuronic acid was ound to be the only moiety ingymnemic acid A1 [ ]. Further, a series o gymnemic acids(gymnemic acid I, II, III, IV, V, VI, and VII) were isolated andcharacterized rom the hot water extract o dry leaves o G.sylvestre [ , ]. Te Gymnemic acids comprise o severalmembers designated as gymnemic acids IVII, gymnemo-sides AF, and gymnemasaponins able . Te derivatives o gymnemic acids are several acylated tigloyl, methylbutyrylgroup substituted members, derived rom deacylgymnemicacid (DAGA) which is a -O- -glucuronide o gymnema-genin ( , , , , , -hexahydroxy-olean- -ene).Gymnemic acid A comprises o gymnemic acids A1 , A2 , A3 ,and A4 and named gymnemagenin. Tis constituent is a D-glucuronide o hexahydroxy-triterpene that esteri es withacids [ ].Other vegymnemic acids,namely, VIII, IX,X, XI,and XII, were isolated and characterized later [ ]. Gymne-masaponins III, another antisweet compound, isolated romG. sylvestre was ound to consist o hydroxylongispino-genin as the aglycone moiety glycosylated with either one ortwo glucose molecules at both the or hydroxyl groups[ ]. Tese compounds exhibited lesser antisweet effect thanthose o gymnemic acids [ ].

Gurmarin, an important amino-acid peptide having amolecular weight o , was isolated rom G. sylvestre [ ].Te sugar suppression activity o this compound was deter-mined electrophysiologically on the taste responses o rat[ ]. Te antisweet effect o thispolypeptide is veryspeci c tosweet taste on tongue, affected by the pH change. It has beenreported that the polypeptide exhibited maximum antisweet-ner property near its isoelectric point [ ]. Te hydrophobic,rather than the ionic, interaction plays a signi cant role inproper binding o gurmarin to the target molecules [ , ].Te other important constituents isolated rom leaves are


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gymnemasins A, B, C, and D and alkaloids [ ]. A num-ber o saponins such as gymnemic acid, deacyl gymnemicacid, gymnemagenin [ ], -hydroxylnogispinogenin, andgymnestrogenin have been puri ed [ , , ] rom G.sylvestre. Te phytochemicals in lea extract were also ana-lyzed through gas chromatography coupled to mass spectro-

metry and identi ed or the presence o terpenoids, glyco-sides, saturated and unsaturated atty acids, and alkaloids inthree different leaves extract, namely, petroleum ether, chlo-ro orm, and methanol as solvents used or extraction [ ].Te bioactive constituents present in the plant were ound tobe mixture o diverse phytomolecules such as gymnemicacids, gymnemosides,gymnemasaponins, gurmarin, gymne-manol, stigmasterol,d-quercitol, -amyrin relatedglycosides,anthraquinones, lupeol, hydroxycinnamic acids, and coum-arols group.

5. Biosynthesis and Genomics

Saponins, natural products widespread in plant kingdom, areglycosides composed o triterpenoids or steroidal aglyconesmoieties [ ] and the aglycones are known as sapogenins.Many plant-derivedsaponins,namely, ginsenosides, soyasap-onins, and saikosaponins have been ound to exhibit signi -cant anticancer activity. Besides, some saponins display phar-macological properties, namely, anticholesterolemic, adjuvant hemolytic, and anticancer [ ]. It was also ound thatthe oods originating rom plants having an increased level o triterpenes are thought to have a cholesterol lowering effect.

ransgenics with altered levelso triterpenes may be resistantto pests and increased saponin content will con er enhancednutritional value to the plant.

riterpenoid saponinsare a classo plantsecondarymeta-bolites originated via the isoprenoid pathway bycyclization o

, -oxidosqualene precursor in which one or more sugarresidues are added [ ] and leading to the ormation o thetriterpenoid skeleton o b-amyrin and related glycosides. Tepresence o polar nucleus, linked to one or more sugarresidues, is responsible or the characteristicactivitieso thesecompounds [ ]. Majority o the signi cant steps at molecu-lar level in triterpenesaponin biosynthesis remain uncharact-erized. Te steps involving the biosynthesiso b-amyrin by b-amyrin synthase, an oxidocyclase, have been well character-ized in several plant species including Arabidopsis thaliana[ ], oat [ ], but steps involving the modi cation o thetriterpenoid backbone by the cytochrome P -dependentmonooxygenases and uridine diphosphate glycosyltrans-

erases remain less understood.Extensive research has gone into the metabolic pro ling

o G. sylvestre, but there are very ew reports pertaining tometabolomics and genomics. Te structural elucidation o gymnemic acid revealed the presence o triterpene aglyconemoiety known as sapogenin attached to a sugar chain. Teoccurrence o signi cant percentage o triterpene glycosidesin plant indicates that glycosylation is a critical process in themodi cation/generation o triterpene saponins. Studies in-cluding the metabolomics and unctional genomics withemphasis on the gene identi cation, cloning, and their

unctional characterization will be an important tool in deci-phering the unctional role o these genes in the biochemicalpathway leading to medicinal properties o the phytocon-stituents in the plant.

Further, in an attempt to understand themolecularmech-anism o genes responsible or medicinal properties o G.

sylvestre, two partial cds (accession nos. GU ;GU )were submittedto NCBI database[ , ]. Furtherstudies into the identi cation and characterization o genesinvolved in the biosynthesis o triterpene glycosides, gym-nemic acids will provide valuable in ormation in decipheringthe biosynthetic pathway o gymnemic acids and the mech-anism o their pharmacological activities in the plant. Since,the transcriptome data o Gymnema sylvestre is unavailableand various proteins and enzymes at the biochemical levelremain uncharacterized, so the exact mechanism o Gym-nemic acid biosynthesisis notreported in the literature. How-ever, extensive research is ongoing in our lab to decode the

unctional role o glycosyltrans erases in biosynthesis o Gymnemic acids owing to its signi cant pharmacologicalimportance (unpublished data). Te biosynthesis pathway o gymnemic acid remains unknown; however, putatively path-way or triterpene glycosides is derived rom the isoprenoidpathway with glycosylation o the triterpene aglycone at theterminal trans ormation o gymnemagenin. A general dia-grammatic sketch has been drawn to represent a putativepathway with a ocus on terminal pathway steps in bio-synthesis o saponins rom Gymnema sylvestre (Figure ).

6. Mechanism of Action of Gymnemic Acids

Te mode o action o the drug is through stimulation ininsulin secretion rom pancreas [ ]. It also exerts a similareffect by delaying the glucose absorption in the blood. Teatomic arrangements o gymnemic acids to the taste buds aresimilar to sugar molecules which ll the receptors in the tastebuds preventing its activation by the sugar molecule in the

ood. Similarly, in the intestine it attaches to the receptor pre-sent in external layer o intestine, thereby preventing theabsorption o sugar molecules by intestine, leading to reduc-tion in blood sugar levels [ ]. Gurmarin acts in a similarmanner by inter ering with the ability o taste buds on thetongue to differentiate between sweet and bitter. Hypoglyce-mic effect o gymnemic acids includes a cascade o eventsstarting rom modulation o incretin activity which triggersinsulin secretion and release. It also increases regeneration o pancreatic islet cells to enhanced enzyme mediated uptake o glucose. Tis process decreased glucose and atty acid assim-ilation in the small intestine and inter eres in the ability o receptors in mouth and intestine to sensation o sweetness. Ithas been previously reported in the literature that the actiono gymnemicacid is similar to that o incretin-mimeticmech-anism o action [ ]. Gymnemic acid has been ound tointeract with glyceraldehyde- -phosphate dehydrogenase(GAPDH), a keyenzyme in glycolysis pathway [ ].Te nd-ings also indicatedthat theacyl moietiespresent in gymnemicacids play important role or the GA-induced smearing o GAPDH and G PDH and play an integral role in the anti-hyperglycemic activity o GA derivatives [ ].


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Mevalonate pathway (cytoplasm)

Mevalonate-5-pyrophosphate

Phosphomevalonate kinase

Mevalonate-5-phosphate

Mevalonic acid

HMG-CoA reductase

3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)

Acetoacetyl-CoA

Acetyl-CoA

Tiolase

HMG-CoA synthase

Mevalonate kinaseA P

A P

2,3 Oxidosqualene

riterpenoids saponins(gymnemic acids, gymnemasinsgymnemasaponins)

Squalene

P450s/G sSqualeneepoxidase

Farnesyl-PP

FPPS

Squalene synthase

Geranyl-PP

IPP

Geranyl phosphatesynthase

DMAPP

Dimethylallyl PP

Isopentenyl-5-pyrophosphate

Mevalonate-5-Pdecarboxylase

Isopentenyl-PP isomerase

CO2

Glyceraldehyde 3-phosphate

Pyruvate DXS

1-deoxy-D-xylulose 5-phosphate DXR

Methyl erythritol phosphate

Isopentenyl-5-pyrophosphate

Dimethylallyl PP

DOXP pathway (plastid)

F : Hypothetical pathway o Gymnemic acid biosynthesis. Te general sketch represents the ormation o triterpenoids throughMevalonate pathway. Further, it was assumed that gymnemagenin (sapogenin) gave rise to gymnemic acids and derivatives throughglycosylation mechanism by glycosyltrans erases.

7. Pharmacological Activities of Extracts and Pure Compounds Isolatedfrom Gymnema sylvestre

Although the herb is widely used as a naturopathic treatmentordiabetes [ , ], it also demonstratespromising effects in

the treatmento obesity, arthritis, hyperlipidemia,Parkinson-ism, and hypercholesterolemia [ ]. Furthermore, thebioactive compounds o plant have antimicrobial, anti-in a-mmatory, and anticancer properties. Te leaves o the plantare used or the treatment o obesity [ ], dental caries [ ],antibiotic, in stomachache,blood puri er, and in rheumatism[ ]. Some o the signi cant pharmacological properties o the herb had been discussed in detail. Various plant parts,namely, leaves, roots possess medicinal properties and used

or the treatment o various diseases in Ayurvedic system o

medicine (supplementary able ). Numerous bioactivecom-pounds isolated rom the plant either as pure compounds oras crude extracts possess medicinal properties and clinically tested in animal model systems or scienti c validation (sup-plementary able ).

. . Antidiabetic Property. Te herb accounts or its sweetinactivation property to the presence o triterpene saponinsknown as gymnemic acids, gymnemasaponins, and gur-marin. Experimental trials con rmed the hypoglycemiceffect o G. sylvestre on beryllium nitrate and streptozotocintreated rats. Tere was a slight increase in body weight andprotein and a signi cant decrease in asting blood glucose indiabetic rats treated with G. sylvestre, C. auriculata , E. jam-bolanum ,and S. reticulata andtheeffectswere quite similar toinsulin and glibenclamide treated mice.


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An investigation to determine the antioxidant activity o Gymnema lea extract and the role o antioxidants in diabeticrats was per ormed by Kang et al. [ ] using ethanolicextracts. Several antioxidant assays, namely, thiobarbituricacid ( BA) assay with slight modi cations, using egg yolk lecithin or -deoxyribose (associated with lipid peroxida-

tion), superoxide dismutase- (SOD-) like activity assay,and , -Azinobis ( -ethylbenzothiazoline- -sul onic acid)(AB S) assay (involved in electron or radical scavenging),depicted signi cant antioxidant activity o the ethanolicextract. Further LC/MSanalysis revealed thepresenceo anti-hyperglycemic compounds like gymnemagenin and gymne-mic acids in G. sylvestre extract and the level o lipid per-oxidation reduced by . % in serum, . % in liver, and . %in kidney in diabetic rats ed with the ethanolic extract. Teactivity o transaminases in gluconeogenesis and ketogenesisin diabetes like glutamate pyruvate transaminase (GP ) inserum and glutathione peroxidase in cytosolic liver returnedto normal levels afer the administration o ethanolic lea extract in diabetic rats [ ]. Antihyperglycemic effect o crude saponin raction and ve triterpene glycosides (gym-nemic acids IIV andgymnemasaponin V), isolated rom themethanolic extract o the leaves, was reported [ ]. It was

ound that gymnemic acid IV ( . / . mg/kg) decreasedblood glucose levels by . . % within hours o admin-istration as compared to glibenclamide. It has been reportedthat gymnemic acid IV increased plasma insulin levels inS Z-diabetic mice at a concentration o . mg/kg while itdidnot cause inhibitoryeffect on -glucosidaseactivity in thebrush border membrane vesicles o small intestine in normalrat.

Similarly, in an experimental study, the antidiabetic andhypolipidemic potential o dried powdered leaves o G. syl-vestre was investigated. Te effect o G. sylvestre lea extractwas administered to nondiabetic and alloxan-diabetic rats. Itwas ound that the Gymnema lea extract had no effect on thealleviated glycemia caused by balanced meal or due to theadministration o glucose or amylose but increased serumlipid level afer SOC treatment. However, in nondiabetic andalloxan diabetic rats the subacute andchronic treatment withGymnema extract had no effect on the ingestion o ood andwater, gain o body weight, andthe levelo glucose andlipidinblood. But the herbal ormulation requires clinical approvaland scienti c validation be ore being used or the treatmento diabetes and hyperlipidemia [ ]. Finally, it was concluded

rom the studies that the herb possesses antidiabetic effectand sugar inactivation properties.

. . Antiarthritic Activity. Te lea extract o G. sylvestre wasexamined or antiarthritic activity on albino rats. Te watersoluble and petroleum ether ( C) extract was ound tobe signi cantly effective in controlling arthritis. It was alsoassumed that the most potent antiarthritic activity o theleavesmaybe due to the nature o triterpenoids, steroids, andsaponin glycosides [ ]. Different extracts were suspendedwith % ween , and the drug Diclo enac sodium wasadministeredonce daily through oral route and the effect wasmonitored or days. Itwasobserved that the rats developed

swelling in multiple joints on induction with an adjuvant andexhibited in ammation in cells, bone destruction, and re-shaping. Te petroleum ether extract treated group showedsigni cant reduction in paw swelling possibly due to inhibit-ing the response o in ammatory cells or blocking the releaseo mediators like cytokines (IL-Ib and NF-a), GM-CSF,

inter erons, and PGDF which are responsible or pain anddisabilities arising due to destruction o bone and cartilage[ ]. Te other possible mechanism o action suggested pro-tection o therelease o joint cartilageandbone destruction inchronic arthritic model [ ]. Te multiple studies employinguse o polar solvents in extract preparations by investigatorsdemonstrated the antiarthritic potential o the lea extract.

. . reatment of Dental Caries. Dental caries can be de nedas in ection o tooth, occurring due to various kinds o gram-positive cariogenic bacteria [ ] like S. aureus, S. mitis, and S.mutans, and ungus-like Candida albicans which attaches tothe tooth sur ace through release o extracellular polysaccha-

rides rom sucrose and metabolize sugar to organic acidmainly lactic acid resulting in demineralization o the toothenamel [ ]. Te chloro orm, petroleum ether, andmethano-lic lea extracts o G. sylvestre at various concentrations o ,

, and mg/mL were testedagainstmicrobialdental in ec-tions and ound to be signi cantlyeffective against these cari-ogenic bacteria particularly the methanolic extract whichshowedhighestactivity atminimum concentration. Te goodpotentialo thehydroalcoholicextract o theplantleadsto thedevelopment and manu acture o gurmar tooth powderedmarketed as Gurmar Herbal tooth paste and Gurmar Her-bal ooth powder. Tese herbal ormulations offer new pro-spects in the treatment o dental caries once clinically ap-

proved by the scienti c community [ ].

. . Antibiotic and Antimicrobial Activity. Te antibiotic andantimicrobial activity o different extracts o G. sylvestre wasdetermined [ ] against a number o pathogens, namely, S.aureus , E. coli, and B. subtilis while no activity was observedagainst gram-negative bacteria. G. sylvestre lea extractsshowed good prospects as an antibiotic herbal remedy waseffective as herbal ormulation or the treatment o microbesrelated in ections[ ]. Te antibacterial activity o G. sylvestreand gymnemic acid was also studied against E. coli and B.cereus and the antimicrobial effect was signi cant against themicrobes [ ]. Bhuvaneswari et al. [ ] demonstrated that the

methanolic extracts o G. sylvestre were assessed or antimi-crobial activity o aerial and root parts separately. Te resultexhibitedthat themethanolextracts in acidicrangehavegoodactivity towardsall thepathogensshowing itsbroadspectrumnature. In a similar study, the antimicrobial effect o ethanolicextract o G. sylvestre against Bacillus pumilus, B. subtilis, P.aeruginosa, and S. aureus showed promising antimicrobialeffect [ ]. It can be in erred rom the studies that the meth-anolic and ethanolic lea extract o Gymnema sylvestre pos-sesses considerable antibiotic and antimicrobial activity.

. . Anti-In ammatory Activity. In the Ayurvedic system o medicine, the lea o G. sylvestre has been widely used and is


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. . Ethnobotanical Uses. raditionally, the leaves o G. sylv-estre were used or the treatment o diabetes and other disor-ders, while the owers and bark are given in diseases relatedto phlegm [ ]. Te ancient literature on Indian medicine,Sushruta, describes gurmar as a destroyer o madhumeha(glycosuria) and other urinary disorders. Te extract o G.

sylvestre is reported to be a bitter acrid, anti-in ammatory,anodyne, digestive, liver tonic, emetic, diuretic, thermogenic,stomachic, stimulant, anthelmintics, laxative, cardiotonic,expectorant, antipyretic, and uterine tonic. Te plant also ex-hibits medicinal importance in the treatment o jaundice,constipation, cardiopathy, asthma, bronchitis, amenorrhoea,conjunctivitis, renal and vesical calculi, dyspepsia, leuco-derma, and Parkinsonism [ ]. Reports in the ancient litera-ture suggested that the plant has multiple medicinal applica-tions, namely, antihelminthic, antipyretic, astringent, an alex-ipharmic, anodyne, cardiotonic, digestive, diuretic, coughdyspepsia, hemorrhoids, hepatosplenomegaly, laxative, stim-ulant, stomachic, uterine tonic, intermittent ever, jaundice,and leucoderma. Te root bark is use ul as an emetic, expec-torant, and analgesic or bodyache and root juice in the treat-ment o snakebite [ ]. Te plant extract is also use ul in thetreatment o piles, colic pain, dropsy, phlegm, eye troubles,cardiac, and respiratory diseases.

8. Bioavailability and Toxicity

Bioavailability is a key issue in terms o effectiveness o any herbalmedicineasa drug andwill determineitseffectivedeli- very into the circulatory system in the body.Bioavailability o gymnemic acid is an important parameter or its in vivophar-macologicalapplications. Gymnemic acidhaspoor lipidsolu-

bility and complex structure and difficult to pass through thebiomembranes or its absorption in circulatory system.Pathan and coworkers have developed a herbal ormulation(gymnemic acid: phospholipid complex) with an aim toimprove its bioabsorption and pharmacokinetics. A phyto-some exhibits betterabsorption andutilization in bodydue toits increased capacity to cross lipid biomembranes and reachthe systemic circulation. Te complex exhibits antiapoptoticpotential in doxorubicin-induced cardiotoxicity in rats andshows cardioprotective effect [ ]. oxicity studies o Gym-nema sylvestre extract have shown its sa ety when takenin recommended doses. High doses may lead to sideeffects including hypoglycemia, weakness, shakiness, exces-

sive sweating, and muscular dystropy. Administration o . % basal powder (GSE) in the diet in Wistar rats or weeks has shown no toxic effects and no animal died duringthe experiment [ ]. reatment o diabetic patients withGymnema sylvestrehas been shown to cause toxic hepatitis ordrug-induced liver injury (DILI) [ ].

9. In Vitro Cultivation of Gymnema sylvestre

Cultured plant cells and tissues are widely recognized as pro-mising alternatives or the production o valuable secondary metabolites [ , ]. Plant tissue culture techniques havebeen employed on an industrial scale or the production o

bioactive compounds [ ]. Various techniques were em-ployed or propagation o the herb in plant tissue culturethrough in vitro multiplication or shoot regeneration rommaturenodal explants o G. sylvestre[ ] and large-scale pro-duction o gymnemic acids in plant cell suspension cultures[ ]. Somatic embryogenesis was optimized and whole plant

regeneration was achieved in callus cultures derived romhypocotyl, cotyledon, and lea explants excised rom seed-lings o G. sylvestre. Globular/heart shaped embryos devel-oped and produced torpedo and cotyledon stage embryosupon subculturing on embryo maturation medium EM(medium containing MS salts, B vitamins, . M BA, and

% sucrose). Te mature embryos were subcultured on reshEM medium or embryo germination and plantlet orma-tion. Tese plantlets were grown in glasshouse, respectively [ ].

For in vitro regeneration o mature nodal explants o G.sylvestre, Murashige and Skoog (MS) media were used or theinoculationo single node explantshaving differentcombina-tions o -benzylaminopurine (BAP) or kinetin with naph-thaleneacetic acid (NAA) and auxins like indoleacetic acid(IAA) alone or in combinations. Te MS medium containingBAP ( mg/L) and NAA ( . mg/L) exhibited maximumnumber o shoot ( per explants). Further, the regeneratedshootswere subjected to rooting onMS hal strength mediumin absence o any growth regulator (IAA, IBA, and NAA). Incultures where the shoot explants were inoculated on auxin-

ree hal strength MS basal medium, root primordia emergedrom the shoot base days afer implantation and sub-

sequently developed into roots without basal callus as com-pared to MS media supplemented with different concentra-tions o auxins, which did not lead to root ormation [ ].

Plant cell suspension cultures were generated or large-scale production o gymnemicacids, theantisweet phytocon-stituents. Te methodology employed led to the developmento a novel cell culture system or in vitro growth and cultiv-ation o this species. Te conditions or the production andHPLC quanti cation o gymnemicacids were optimized. Tegymnemic acids were not accumulated in callus but werereleased into the medium. For the production o gymnemicacid commercially, this needs to be urther optimized. Inanother study, theextraction o gymnemicacid through gym-nemagenin rom callus culture o G. sylvestre was reported.Te aglycon component, known as gymnemagenin, wasextracted, detected, andquanti ed in different calluscultureso G. sylvestre. HP LC methodwasstandardized or therapidand accurate quantitative estimation o gymnemagenin incallus cultures o G. sylvestre [ ].

Recently, Devi and Srinivasan [ ] attempted the large-scale production o gymnemic acids under in vitro condi-tions, through the mediation o ungal elicitors. Te use o bioelicitors, such as Aspergillus niger cell extract, enhancedthe production o secondary metabolite, namely, gymnemicacids rom G. sylvestre suspension culture. It is interestingto note that the elicitation o Gymnema suspension cultureby A. niger signi cantly enhanced the production gymnemicacid as compared to nonelicited cultures. Te technique is apotential means or the establishment o large-scale produc-tion o gymnemic acids through the employment o shaking


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ask andbioreactors. Due to the limited availability o G. sylv-estre ormulation, this technique holds good prospects orlarge-scale commercial production o bioactive phytocon-stituents [ ].

Gymnemic acid being an important bioactivecompound,cell suspension cultures o G. sylvestre were generated and

optimized or the production o gymnemic acids [ , ].

10. Summary and Future Prospects

Medicinal plants served as a plat orm or ancient Ayurvedicsystem o medicine. In the present scenario, herbal therapeu-tics are gaining momentum in pharmacological applicationsandas moleculartargets in thedrug development. Teemerg-ing trend in rising incidence o diseases and associated com-plications with commercial medications poses a seriousthreat to mankind. Naturopathic treatments offer respite

rom the high costo expensivedrugs aswell as in beingcom-paratively sa e with less side effects. It is estimated that nearly

%o population depends on thenatural remedies orhealthcare. Plants are a valuable source o a number o bioactivecompounds like alkaloids, quinine, paclitaxel, opium alka-loids, quinine, atropine, and cardiac glycosides (digitalis,ouabain) to name a ew. Te rst antidiabetic drug, met or-min, isolated rom Galega officinalis, was a herbal ormula-tion. Tus, it becomes very important to screen plants withpharmacological signi cance as a basis or the developmento newer and more effective therapeutics. In spite o the goodprospects o herbal medicines, these have gained little impor-tance due to absence o scienti cvalidation. Te lack o avail-ability o standards or herbal ormulations is a major limita-tion. Although, a vast repertoire o plant resources is availablebut very ew have experimentally validated and scienti cally approved as medications or the treatment o diseases.

One major actor that comes into play is that many medi-cinal plants o commercial importance ace threat o extinc-tion due to increase in demand and destruction o their habi-tats due to urbanization and industrialization. Te primeinitiative should ocus on the cultivation and conserva-tion o medicinal plants with pharmacological importance.Although, the herb has immense prospects in drug develop-ment, but it aces threat o extinction dueto continuous de or-estation and absence o established lines or varieties. Te invitro propagation o plants, in plant tissue culture offers apromising alternative or the production o valuable sec-ondary metabolite. G. sylvestre, being a valuable medicinalplant and source o bioactive substances, needs to be propa-gated and conserved. In vitro propagation o plants with highbioactive content and cell culture technologies or large-scaleproductiono suchsecondarymetabolites withmedicinal sig-ni cance will be highly prospective and will provide new dimensions to this area o research. Studies have been madein the past ew years to understand the complex and incom-pletely understoodnature o plant cells in vitro cultures [ ].Bioelicitors based strategies ( rom Xanthomonas spp. and A.niger cell extract) or enhanced production o gymnemicacids have been employed [ , ], and the technique ndsrelevance or large-scale production o these bioactive com-pounds in bioreactors based industrial applications. Tese

new technologies will be new beginning or urther produc-tion and utilization o these sweet suppressing compoundsinvaluable as an antidiabetic herbal cure.

G. sylvestre holds a unique position among the sweetnessmodi ying materials o natural origin. Te herb accounts ormultiple pharmacological signi cance as a naturopathic

medication since ancient times and gaining popularity in thepresent scenario as well.Various polyherbal ormulations likeDihar [ ] and D- [ ] containing G. sylvestre extracthave been used or the treatment o diabetes mellitus. Severalclinical trials and experimental studies indicated that theplant is an invaluable source o bioactive compounds andphytoconstituents like gymnemic acids have been used asmolecular targets in drug development. Besides having phar-macological importance, the herbal extract exhibits goodprospects in dietary applications. G. sylvestre dried lea powder is orallyconsumed by Paliyan tribes o Sirumalai hills

or treatmento diabetes. Several products such as GNCHer-bal Plus Standardized G. sylvestre (herbal supplement), Vita-min Shoppe G. Sylvestre (sugar destroyer), Gymnema gold(Nutrigold) abolishe the taste o sugar and help supporthealthy glucose; Gurmar capsules (stimulates the heart andcirculatory system and activate uterus) are some o the pro-ducts composed o Gymnema extract and are marketed andsold as herbal preparations. Among the medicinal plants, G.sylvestre is a herb less exploited or its innumerable advan-tages. Te aim o this review is to highlight the prospects o this rare herb as a potential medication or treatment o dis-eases rom diabetes, obesity to cardiovascular disorders aswell as a very good dietary and health supplements in oodindustry as an health tablets, beverages, tea bags, energy sup-plements, and in ood items which regulates body weight.Gymnema sylvestre is a herbal preparationwhich contains

% Gymnemic acid rom lea extract and provides nutri-tional support to pancreas and maintain healthy blood sugarbalance when used as part o diet.

Te whole genome sequencing projects and unctionalelucidation o pathway genes have made signi cant contribu-tions in deciphering the biological role andproperties o bio-molecules. With the unctional characterization o genes,their relevance in the plant and unctional role in the bioac-tivity o phytomolecules are being established. In ormationabout such genes which code oreconomically viable traitsorpharmacologically importantbioactive molecules holdsgreatprospects in crop engineering. Te development o genetictrans ormation systems will provide an edge in the propaga-

tion and maintenance o such pharmacologically importantplant having applications in drugdiscovery anddevelopment.

Acknowledgments

Te authors are thank ul to CSIR Network Project NWPor the nancial grant. Pragya iwari thanks CSIR, New

Delhi, or the award o Senior Research Fellowship.

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