Urankar et al. UJP 2013, 02 (06): Page

Universal Journal of Pharmacy, 02(0

*Corresponding author: Manohar Urankar Sr. Manager - Oral Care R&D,

Kemwell Biopharma Pvt. Ltd.,

"Kemwell House", 11, Tumkur Road, Yeshwantpur,

Bangalore-560022, INDIA.

Mobile: +91-80-9740068595

Email: manohar.urankar@kemwellpharma.com

Universal Journal of PharmacyTake Research to New Heights

REVIEW ON MEDICINAL HERB GENUS SPILANTHES ANDAPPLICATIONS IN ORAL HYGIENE

Manohar Urankar

Kemwell Biopharma Pvt

Received 15-12

ABSTRACT

The therapeutic use of medicinal plant has gained considerable momentum in the worldoveruse of synthetic drugs resulting in higher incidence of adverse reaction has motivated mankind to search for an alternative bioactive product for oral cavity.In recent years, many new compounds of genus Spilanthes herb havanalgesic, antibacterial and anti-inflammatory activity. The present review aims to compile an upemphasis on ethno medical uses, phytochemical, scientific documents of pharmacological activities with respect to oral care diseases. This review explores extracts, phytochemicals & formulations of Spilanthes evaluated for possible analgesic, anti-inflammatory, antioxidant activity. Howeverresearchers in different disciplines. One must make the best use of the naturally available resources which provide valuable raw material for advanced oral care research.Keywords: Bioactive, Spilanthes, Analgesic, Oral Hygiene, Toothache.

INTRODUCTION

Pain is the most important symptom that brings the patient to physician. Analgesics relieve pain as a symptom, without affecting its causegeneration of reactive oxygen species (ROS) and other radicals can damage proteins, carbohydrates, polyunsaturated fatty acids, and DNA, and may thus lead to oxidative stress and to a variety of degenerative processes and diseases such as aging, immune deficiencies, neurologic disorders, inflammation, arthritis, ischemia, arteriosclerosis, coronary heart disease, stroke, diabetes mellitus, Parkinson’s disease, Alzheimer’s disease and certain cancers2,3. ROS are continuously produced during normal physiologic events and removed by antioxidant defense mechanisms. Therefore, the great interest has been recently focused on the natural foods, medicinal plants and phytoconstituents due to their well known

): Page 25-33

Journal of Pharmacy, 02(06), Nov-Dec 2013

"Kemwell House", 11, Tumkur Road, Yeshwantpur,

Universal Journal of PharmacyTake Research to New Heights

EDICINAL HERB GENUS SPILANTHES ANDAPPLICATIONS IN ORAL HYGIENE

Manohar Urankar, Anand Desai and Ramachandra Bhat

Kemwell Biopharma Pvt. Ltd., 11, Tumkur Road, Yeshwantpur, Bangalore-560022, INDIA

12-2013; Revised 20-12-2013; Accepted 24-12-2013

The therapeutic use of medicinal plant has gained considerable momentum in the world during the past decade. The overuse of synthetic drugs resulting in higher incidence of adverse reaction has motivated mankind to search for an alternative bioactive product for oral cavity. In recent years, many new compounds of genus Spilanthes herb have been established. Spilanthol is known to possess

inflammatory activity. The present review aims to compile an up-to-date and comprehensive information on genus Spilanthes with special

tochemical, scientific documents of pharmacological activities with respect to oral care diseases. This review explores extracts, phytochemicals & formulations of Spilanthes evaluated for possible

inflammatory, antioxidant activity. However there are many gaps which need to be filled by concurrent researchers in different disciplines. One must make the best use of the naturally available resources which provide valuable raw material for advanced oral care research.

nthes, Analgesic, Oral Hygiene, Toothache.

Pain is the most important symptom that brings the patient to physician. Analgesics relieve pain as a symptom, without affecting its cause1. Excessive generation of reactive oxygen species (ROS) and other

damage proteins, carbohydrates, polyunsaturated fatty acids, and DNA, and may thus lead to oxidative stress and to a variety of degenerative processes and diseases such as aging, immune deficiencies, neurologic disorders,

arteriosclerosis, coronary heart disease, stroke, diabetes mellitus,

Alzheimer’s disease and certain . ROS are continuously produced during

normal physiologic events and removed by antioxidant the great interest has

been recently focused on the natural foods, medicinal plants and phytoconstituents due to their well known

abilities to scavenge free radicals (i.e. antioxidant power)4. Now-a-days attention is being focused on the investigation of the efficacy of plantin the traditional medicine because they are cheap, have little side effects. According to WHO, about 80% of the world population still rely mainly on herbal remedies5. Among the reported plants, leaves were the dominpart in oral care uses (25.44%), followed by root (20.17%), as represented in Pie chart of Figure 1.

Figure 1: Useful Plant Parts (%)

Use of plant based products in various types of oral care problems is as depicted in below graph2.

ReviewISSN 2320

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25

EDICINAL HERB GENUS SPILANTHES AND ITS

560022, INDIA

during the past decade. The overuse of synthetic drugs resulting in higher incidence of adverse reaction has motivated mankind to search for an

e been established. Spilanthol is known to possess

date and comprehensive information on genus Spilanthes with special tochemical, scientific documents of pharmacological activities with respect to oral

care diseases. This review explores extracts, phytochemicals & formulations of Spilanthes evaluated for possible there are many gaps which need to be filled by concurrent

researchers in different disciplines. One must make the best use of the naturally available resources which provide

abilities to scavenge free radicals (i.e. antioxidant

days attention is being focused on the he efficacy of plant-based drugs used

in the traditional medicine because they are cheap, have little side effects. According to WHO, about 80% of the world population still rely mainly on herbal

Among the reported plants, leaves were the dominant part in oral care uses (25.44%), followed by root (20.17%), as represented in Pie chart of Figure 1.

Figure 1: Useful Plant Parts (%)

Use of plant based products in various types of oral care problems is as depicted in below graph6 of Figure

view Article ISSN 2320-303X

Urankar et al. UJP 2013, 02 (06): Page

Universal Journal of Pharmacy, 02(0

Figure 2: Usages Of Traditional Oral Care Plants

One of very interesting herbal ingredient that can reduce the toothache caused due to tooth sensitivity is flowers of naturally occurring plant: Spilanthes Acmella (Botanical Name) Spilanthes Acmella is popularly known in the world as toothache-plant because by chewing the leaves or flowers, it produces a numbing effect on the tongue and gums. Acmella oleraceae also known by Spilanthus acmella and Spilanthus oleraceae is an importantmedicinal plant with rich source of therapeutic constituents. The flower heads of S. acmella can be used to relieve toothache and also as anti-inflammatory and analgesic7. Spilanthes acmella L. (tooth- ache plant) is an annual herb belonging to the family Compositae. The genus is widely distributed throughout the tropics and subtropics and can be found in damp pastures, at

Table 1: Traditional uses of different parts of Spilanthes

PHYTOCHEMISTRY: The active constituent spilanthol chiefly present in leaves and flower heads produce analgesic activity to numb toothache. The analgesic activity of spilanthol has been attributed to an increased Gama amino butyric acid (GABA) release in the temporal cerebral cortex14. Interestingly, spilanthol has been

Part used

Flowers Relieve toothache, Cure paralysis of tongue, Remedy for stammering, in treatment of scabies, psoriasis, scurvy, infections of gums, periodontosis, stammering in children and in mouthwashes.

Leaves Stimulant, Sialagogue, Local anaesthetic, immunomodulatory, adaptogenic, toothpaste, lithotriptic, antiscorbitic, Sialagogue, antibacterial and digestive

Roots In headache, Asthma, Rheumatism, treatment of scabies, psoriasis, scurvy, infections of gums, periodontosis, paralysis of tongue and remedy for stammering in children and in mouthwashes.

Whole plant In treatment of dysentery and

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Journal of Pharmacy, 02(06), Nov-Dec 2013

Usages Of Traditional Oral Care Plants

One of very interesting herbal ingredient that can reduce the toothache caused due to tooth sensitivity is

Spilanthes Acmella

Spilanthes Acmella is popularly known in the world as because by chewing the leaves or

flowers, it produces a numbing effect on the tongue and gums. Acmella oleraceae also known by Spilanthus acmella and Spilanthus oleraceae is an important medicinal plant with rich source of therapeutic constituents. The flower heads of S. acmella can be

inflammatory

ache plant) is an annual Compositae. The genus is

widely distributed throughout the tropics and subtropics and can be found in damp pastures, at

swamp margins, on rocks near the sea and as a weed of road-sides and cultivations. The flower heads were chewed to relieve the toothachrelated complications. Leaves are used externally in treatment of skin diseases. Root decoction is used as purgative. Leaf decoction is used as diuretic and lithotriptic. Whole plant is used in treatment of dysentery8. Preliminary studiesdiuretic14, anti-inflammatory and analgesicvasorelaxant and antioxidantis one of the active ingredients in compositions for acute- or long-term treatment of microbial infections, particularly, oral pathogenic caries, periodontosis, gum disease, gum bleeding and/or plaque reduction10. Around 60 species of genus Spilanthes have been reported from different regions of the world11. Out of these, five species occur in India namely S. acmella Murr, S. acmella L. var. oleraceae Clarke, S. calva L., S. paniculata L., and S. mauritiana L12.

ETHNO MEDICINAL USES: In India, the traditional uses of Spilanthes according to the parts of the plant used 13are presented in Table 1.

Table 1: Traditional uses of different parts of Spilanthes

The active constituent spilanthol chiefly present in leaves and flower heads produce analgesic activity to

The analgesic activity of spilanthol has been attributed to an increased Gama amino butyric acid (GABA) release in the temporal cerebral

. Interestingly, spilanthol has been

demonstrated to inhibit nitric oxide (NO) production in a murine macrophage cell line, to efficiently downregulate the production of inflammatory mediators Interleukin-1 beta (IL-1b), Interleukin (ILnecrosis factor ( TNF-α) and to attenuate the expression of Cyclooxygenase (COXnitric oxide synthase (iNOS)15.

Traditional uses

Relieve toothache, Cure paralysis of tongue, Remedy for stammering, in treatment of scabies, psoriasis, scurvy, infections of gums, periodontosis, paralysis of tongue and remedy for stammering in children and in mouthwashes.

Stimulant, Sialagogue, Local anaesthetic, immunomodulatory, adaptogenic, toothpaste, lithotriptic, antiscorbitic, Sialagogue, antibacterial and digestive

In headache, Asthma, Rheumatism, treatment of scabies, psoriasis, scurvy, infections of gums, periodontosis, paralysis of tongue and remedy for stammering in children and in mouthwashes.

In treatment of dysentery and rheumatism

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swamp margins, on rocks near the sea and as a weed of sides and cultivations. The flower heads were

chewed to relieve the toothache and other mouth related complications. Leaves are used externally in treatment of skin diseases. Root decoction is used as purgative. Leaf decoction is used as diuretic and lithotriptic. Whole plant is used in treatment of

. Preliminary studies have reported as inflammatory and analgesic7,

9. The Spilanthes acmella is one of the active ingredients in compositions for

term treatment of microbial infections, particularly, oral pathogenic microorganisms, dental caries, periodontosis, gum disease, gum bleeding

. Around 60 species of genus Spilanthes have been reported from different regions of

. Out of these, five species occur in India urr, S. acmella L. var. oleraceae

Clarke, S. calva L., S. paniculata L., and S. mauritiana

In India, the traditional uses of Spilanthes according to are presented in Table 1.

demonstrated to inhibit nitric oxide (NO) production in a murine macrophage cell line, to efficiently down-regulate the production of inflammatory mediators

1b), Interleukin (IL-6) and Tumor α) and to attenuate the

expression of Cyclooxygenase (COX-2) and inducible .

Reference No.

43, 44, 25,

26, 45, 46

43, 44, 25

54

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Universal Journal of Pharmacy, 02(06), Nov-Dec 2013 27

Several secondary volatile metabolites like sesquiterpenes, alkamides and oxygenated compounds have been isolated and identified in S. Americana16. However, the most abundant alkamide found was spilanthol. The formula of spilanthol was determined as (2E, 6Z, 8E)-N-isobutylamide-2, 6, 8-decatrienamide17. It is present in the roots, flower heads and whole aerial parts of genus spilanthes18. The flower heads and root part of the plant genus have been reported to be especially rich in this active principle content19. Spilanthol has a strong pungent taste; it may produce local stringency and anesthetic effects20. The structure of spilanthol and three other alkamides isolated from the flower head of S. acmella Var. oleraceae has been determined by spectroscopic methods21. In another study, structures of the pungent alkamides of S. acmella L. were determined by using nuclear magnetic resonance spectroscopy and high-performance liquid chromatography-mass spectrometry (HPLC-MS) with atmospheric-pressure chemical ionization and electron-impact ionization and electron-impact ionization22. The structures of some alkamides are given below.

(2E, 4Z)-N-isobutyl-2,4-undecadiene-8,10-diynamide

(2Z)-N-isobutyl-2-nonene-6,8-diynamide

(2E,6Z,8E)-N-(2-methylbutyl)-2,6,8-decatrienamide

(Spilanthol)

The potential of the extract of S. paniculata as acute anti-inflammatory agent may be due to the presence of phytoconstituents like flavonoids (high amount), tannins etc. Again, no mortality was recorded in the acute toxicity test; it showed that the plant might be safe for use. Therefore, it can be revealed that the ethanolic extract of S. paniculata leaves possess acute anti-inflammatory activity and justify its use as a traditional folk remedy for toothache, pain etc. However, a more extensive study is necessary to determine the exact mechanism(s) of action of the extract and its active compound(s) 23. The leaves contain alkaloids, carbohydrates, pungent amide, tannins, steroids, carotenoids, provitamin A, α-carotene and β-carotene, essential oils, sesquiterpenes, and amino acids etc21, 24. Chemical

analysis shows that Spilanthes acmella contain major pungent compound, spilanthol (N-isobutyl-2E, 6Z, 8E-decatrienamide) which is naturally occurring insecticide, and Butylated Hydroxytoluene. Antioxidant, butylated hydroxytoluene (BHT) and fatty acids (n-Hexadecanoic acid and tetradecanoic acid) could be obtained from extracts of mother plant of flower heads25. The leaves contain alkaloids, carbohydrates, pungent amide tannins, steroids, carotenoids, essential oil, amino acid etc26. The pungent flavour of Spilanthes acmella is due to an unsaturated alkamid, spilanthol which present in its highest concentration (1%) in the flowers. Essential oil was isolated from the flower of S. acmella, whose main constituents were limonene, β-caryophyllene, Z-β-ocimene, γ-cadinen, thymol, germacrene D and myrcene27. The different fractions were isolated from crude ethyl acetate extract of S. acmella and were studied against 27 strains of microorganisms. The results showed that fraction E3 completely inhibited the growth of Corynebacterium diphtheria with minimum inhibitory concentration (MIC) value of 128µg/mL28. PATENTS ON SPILANTHES HERB: US patent application 2009/0155445 A1 reveals a compositions capable of providing stimulation of the trigeminal nerve to induce sensations of the cooling, warming, tingling and salivating type in the animal and human mouth and claimed to achieve a synergistic effect between mixtures of well-known acidulants with a tingling ingredient of Jambu oleoresin or spilanthol. EP 1454 533 A1 discloses products that promote saliva generation in the mouth, through the use of various food grade acceptable acids, in foods such as chewing gums, breath films, toothpaste and lozenges. It discloses in particular food grade compositions comprising a flavoring component, the flavoring component containing at least eight weight percent acid or acid salts selected from the group consisting of citric, malic, adipic, tartaric, Glutaric and fumaric acids; wherein the food grade composition spends at least one minute in the mouth. US patent application 20030118628 A1 addresses the issues related to the xerostomia conditions and the need to provide products capable of alleviating them, discloses confectionery in the confectionery product. The confectionary base may be a carbohydrate or carbohydrate derivative, namely a sugar and the salivation agents include acidulants, cooling compounds, salts, salt enhancers, monosodium glutamate (MSG), MSG enhancers, flavors and mixtures thereof. Mixtures of acidulants include citric acid, malic acid, succinic acid and adipic acid. US patent 3720762 comprises compositions containing at least one of the materials, spilanthol or the isomers thereof formed in the plants of Spilanthes oleraceae Jacquin or Spilanthes acmella Var, oleraceae or the

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crude fractions obtained from the said Spilanthes oleraceae Jacquin or Spilanthes acmella var. oleraceae by extraction or distillation. The spilanthol materials may be combined with each other or with conventional flavoring materials having a cooling effect as composite flavors to be used in dentifrices, mouthwashes, foods, chewing gum, breath fresheners, cough drops, cigarettes and the like to provide compositions for oral use which afford a strong and lasting cooling sensation, a slight sharp flavor which promotes salivation and stimulates the appetite, to effect analgesic activity due to local anesthetic property, thus making tooth brushing more comfortable in the case of suffering from toothache and to provide a suitable flavor for breath fresheners, mentholated cigarettes, cough drops, foods and the like. US patent 6264926 B1 relates to a novel synergistic herbal composition useful as toothpowder and comprising the powders of Zanthoxylum sp, Zingeber offininale, sandal wood, roasted alum, common salt, spilanthes sp., Pistacia sp., Quercus sp., Usnea sp., in the proportion 20-25%, 25-30%, 8.25-8.5%, 8-9%, 15-16.5%, 2-2.5%, 2-2.5%, respectively. As the ingredients are derived from herbal source, it is safe ecofriendly and does not produce harmful results. It is useful for treatment of swollen gums, yellow/staining of teeth, foul odour of mouth and sensitivity to hot and cold water and toothache. US patent 6899901 B2 directs to a sensate composition including at least one cooling sensate, warming sensate and tingling sensate. The tingling sensate is at least one of Jambu Oleoresin and Spilanthol. The present invention is further directed to a method of using the sensate composition in a food, pharmaceutical or personal care product. US patent application 2010/0184863 A1 provides a synthetic spilanthol flavor composition that includes (2E,6Z,8E)-N-(2-methylpropyl)-2,6,8-decatrienamide. The synthetic spilanthol composition can also contain and atleast one of (2E, 6E, 8E)-N-(2-methylpropyl)-2,6,8-decatrienamide and (2E, 6E, 8E)-N-(2-methylpropyl)-2,6,8-decatrienamide being present in amounts effective to impart a salivating or tingle effect while reducing the perception of off notes, as compared to the off-notes, perceived upon consumption of natural spilanthol. Methods of increasing salivation and/or providing a tingling sensation upon consuming an orally consumable product that include a synthetic spilanthol flavor composition are also provided, but not limited to, foods, beverages, pharmaceuticals, nutraceuticals, or therapeutic compositions, oral personal care products, gums (e.g. chewing gum or bubble gum), candy or lozenges. PRECLINICAL STUDIES ON SPILANTHES HERB: The effect of Spilanthes acmella Murr. extracts on Phenylephrine-induced contraction of rat thoracic

aorta as well as their antioxidant activity. Results show that the extracts exert maximal vasorelaxation in a dose-dependent manner, but their effects are less than acetylcholine-induced nitric oxide (NO) vasorelaxation. Significant reduction of vasorelaxation is observed in both NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin (INDO). In the presence of L-NAME plus INDO, synergistic effects are observed, leading to loss of vasorelaxation of both acetylcholine and the extracts. Similarly, the vasorelaxation of the extracts are completely abolished upon the removal of endothelial cells. This demonstrates that the extracts exhibit vasorelaxation via partially endothelium-induced NO and prostacyclin in a dose-dependent manner. Significantly, the ethyl acetate extract exerts immediate vasorelaxation (ED50 76.1 ng/mL) and is the most potent antioxidant (DPPH assay). The chloroform extract shows the highest vasorelaxation and antioxidation (SOD assay). These reveal a potential source of vasodilators and antioxidants29 Spilanthol showed interesting bioactivities, e.g. strong local anesthetic30, analgesic32. Spilanthes acmella Murr. (Compositae) has been used as a traditional medicine for toothache, rheumatism and fever. Its extracts had been shown to exhibit vasorelaxant and antioxidant activities. Herein, its antimicrobial, antioxidant and cytotoxic activities were evaluated. Agar dilution method assays against 27 strains of microorganisms were performed. Results showed that fractions from the chloroform and methanol extracts inhibited the growth of many tested organisms, e.g. Corynebacterium diphtheriae NCTC 10356 with minimum inhibitory concentration (MIC) of 64-256 µg/mL and Bacillus subtilis ATCC 6633 with MIC of 128-256 µg/mL. The tested fractions all exhibited antioxidant properties in both DPPH and SOD assays. Potent radical scavenging activity was observed in the DPPH assay. No cytotoxic effects of the extracts against KB and HuCCA-1 cell lines were evident. Bioassay-guided isolation resulted in a diverse group of bioactive compounds such as phenolics [vanillic acid (2), trans-ferulic acid (5) and transisoferulic acid (6)], coumarin (scopoletin, 4) and triterpenoids like 3-acetylaleuritolic acid (1), β-sitostenone (3), stigmasterol and stigmasteryl-3-O-β-D-glucopyranosides, in addition to a mixture of stigmasteryl-and β-sitosteryl-3-O-β-D-glucopyranosides. The compounds 1–6 represent bioactive metabolites of S. acmella Murr. those were never previously reported. Our findings demonstrate for the first time the potential benefits of this medicinal plant as a rich source of high therapeutic value compounds for medicines, cosmetics, supplements and as a health food33. S. Acmella was evaluated for anti-inflammatory action by Carrageenan-induced rat paw edema. The analgesic activity was tested by acetic acid-induced writhing response in albino mice and tail flick method in albino

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rats. The aqueous extract of S. Acmella in doses of 100, 200 and 400mg/kg showed 52.6, 54.5 and 56.1% inhibition of paw edema respectively at the end of three hours and the percentage of protection from writhing was 46.9, 51.0 and 65.6 respectively. In the tail flick model, the aqueous extract of S. acmella in the above doses increased the pain threshold significantly after 30 min. 1, 2 and 4 h of administration. S. acmella showed dose-dependent action in all the experimental models7. The antioxidant activity of methanol extract of stem and leaves of S. acmella were measured using DPPH and superoxide radical scavenging assays34. The result showed the methanol extract of stem of S. acmella to have the highest superoxide radical scavenging activity while leaves showed maximum DPPH scavenging activity35. In superoxide radical scavenging assay, highest radical scavenging activity was observed in stem and callus, while minimum superoxide radical scavenging activity was found in roots. In DPPH radical scavenging activity was found maximum in leaf and minimum in root. Callus showed significant DPPH radical scavenging activity34. Different doses of aqueous extract of fresh flowers were orally administered to male rats and their analgesic potential was determined at different post treatment periods by using hot plate and tail flick tests. The analgesic activity is mediated supra-spinally accompanied with sedation36. Aqueous extract of ariel part of S. acmella, in experimental animal models showed dose-dependent inhibition of paw edema and increased pain threshold indicating significant anti-inflammatory and analgesic properties37. Spilanthol shows significant anti-inflammatory activity on lipopolysaccharide-activated murine macrophage model RAW 264.7, partly from inactivation of NF-KAPPA B which negatively regulates production of pro-inflammatory mediators38, 39. Drug loaded ethosomes prepared using phospholipid and ethanol, were optimized and characterized for entrapment efficiency, vesicular size, shape, in vitro skin permeation, and stability. The ethosomal vesicles were incorporated in carbopol gel base and its anti-inflammatory efficiency was compared with the marketed diclofenac gel. Mucoadhesive oral gels containing extract were formulated using different concentrations of polymers and extracts and tested for parameters like viscosity and mucoadhesive behavior. The optimized formulation was evaluated for antimicrobial activity against different microorganisms responsible for causing tooth decay using well diffusion method. The results fully validate the claims of the traditional medicine about the use of Akkalkara for local anti-inflammatory and anti-microbial properties and confirm the suitability of ethosomes for transdermal delivery of active constituents of this herbal formulation. Both formulations show results

comparable to that of standard allopathic formulations. The investigation is evaluated for the potential of novel vesicular carrier, ethosomes, containing the methanolic extract of Spilanthes acmella, for anti inflammatory action via transdermal route and to test the potential of the herbal extract for antimicrobial property when formulated as an oral mucoadhesive gel40. The local anesthetic action of ethanol extract of Spilanthes acmella was studied in guinea pigs and frog’s sciatic nerves, subcutaneous injection of 0.1ml of 10% test solution in to guinea pig’s back revealed that the onset of action occurred immediately after injection and lasted for 21 minutes. The Duration of action was significantly shorter than that of 2% lidocaine (p<0.001). The action potential of isolated frog’s sciatic nerve was completely abolished within 5 minutes after application of the test solution. The tissue specimen obtained from guinea pig’s back muscle showed mild congestion of small blood vessels and mild intercellular edema. There was no significant difference as comparing to lidocaine injection. Results indicated that Spilanthes acmella possessed local anesthetic activity and further clinical trial should be investigated41. Sedative potential of the extract was evaluated by using rat hole board technique. The extract was well tolerated. A dose dependent analgesic activity with an EC50 =313 mg kg-1 was evident when evaluated in hot plate but not in tail flick test. This analgesic activity had a rapid onset and short duration of action and was not blocked by naloxone, an opioid receptor antagonist. The mid dose of the extract also induced significant sedation. It is concluded that the analgesic activity is mediated supra-spinally accompanied with sedation. In this study, the analgesic potential of fresh flowers of Spilanthes acmella Murr. Family (Compositae) used by some Srilankan traditional medical practitioners to suppress toothache. The Different doses of water extracts of fresh flowers (111, 335 and 671 mg kg-1) were orally administered to male rats and their analgesic potential was determined at different post treatment periods by using hot plate and tail flick tests42. The total phenolics and alkaloid contents were quantified by using gallic acid and atropine are as standards and antioxidant activity was evaluated by using three free radicals (Superoxide, Hydroxyl and DPPH). Spilanthes acmella extracts revealed the presence of different phytochemical constituents like steroids, terpenoids, flavonoids, alkaloids, glycosides, tannins, carbohydrates, oils and amino acids. The methanol extract have more phenolics and alkaloid contents i.e. 38.83±0.68 (mg/gm) and 26.37±0.16 (mg/gm) than other extracts. The extracts were produced concentration dependent percentage inhibition on free radicals and produced maximum activity at concentrations of 320 and 640µg. Among all

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extracts, methanolic extract showed better activity compared to other extracts with mean IC50 values on superoxide, hydroxyl and DPPH radicals were 189g, 153g and 313g. The above results suggest that Spilanthes acmella extracts have antioxidant activity. Phytochemical analysis, quantification of total phenolics, alkaloid contents and antioxidant activity of Spilanthes acmella extracts (70% Ethanol, Methanol, Ethyl Acetate and Hexane) were evaluated35.

The genus Spilanthes includes many plant species that are being used for the treatment of various disorders. Researchers have done different in-vivo and in-vitro pharmacological screenings to authenticate the traditional uses. These studies have revealed the potential of the plant to be developed as a curative agent from natural resources. Reported pharmacological activities of different Spilanthes species are reported in Table 2.

Table 2: Pharmacological activities of different Spilanthes species

Pharmacological activity

Species Part used

Type of extract

Models used Reference

No.

Antioxidant

S. acmella Murr.

Aerial parts

Chloroform, hexane, ethyl

acetate, Methanol

2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase

(SOD) assay 9

S. acmella Murr.

Leaves, stems

Methanol DPPH, SOD assay 47

Anti-inflammatory

S. acmella Aerial parts

Aqueous Carrageenan-induced paw edema

in rats 7

S. acmella Aerial parts

Ethanol Lipopolysaccharide-activated murine macrophage model

53

Local anesthetic S. acmella L. Murr.

NA Aqueous Xylocaine-induced guinea pig and

frog 37

Analgesic S. acmella Aerial parts

Aqueous Acetic acid-induced writhing

responsein albino mice 7

Antimicrobial

S. paniculata

leaves NA

Bacillus subtilis, Staphylococcus aureus, Enterococcus faecalis, Escheerichia coli, Pseudomonas

aeruginosa, Candida albicans and Microsporum gypseum

48

S. americana

Whole plant

Aqueous, ethanol and

hexane

Staphylococcus aureus, Streptococcus hemolytic, Bacillus cereus, Pseudomonas aeruginosa

and Escherichia coli

49

S. mauritian

a

Roots and

flowers NA

Staphylococcus, Enterococcus, Pseudomonas, Escherichia and

Klebsiella, Salmonella 50

S. acmella Linn.

flower heads

Petroleum ether

Fusarium oxysporium, F. moniliformis, Aspergillus niger

and A. paraciticus 18

S. mauritian

a

Roots and

flowers NA

Candida species and Aspergillus species

51

S. calva Roots Methanol Oral microflora: Streptococcus

mutans, Lactobacillus acidophilus and Candida albicans

52

CONCLUSION

Literature research afforded several plants (single or poly-herbal), extracts and active constituents with significant anti-inflammatory activity. Majority of the active constituents, were identified as alkaloids, flavonoids and rarely xanthones and sterols. Experts

are of the view that there is no acute shortage of leads for developing anti-inflammatory drugs. We need to initiate pending work on these phyto-constituents with emphasis on side-effect profile. Splinthes plant holds great promise as a commonly available medicinal plant and it is indeed no surprise that the plant is referred to in the Indian traditional

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Universal Journal of Pharmacy, 02(06), Nov-Dec 2013 31

circles. From the available literature on various aspects of the plant - traditional to biochemical and ethno botanical to pharmacological - there are many gaps which need to be filled by concurrent researchers in different disciplines. One must make the best use of the naturally available resources which provide valuable raw material for advanced research. After the study of chemical based oral products and plant based products it is obvious that use of plant based or herbal products is safer than & as effective as chemical based products. Due to adverse effects of chemical based remedies and high cost search for alternative products still continues and the phytochemicals isolated from the plants proves to be a good alternative. The present review is an attempt to create an interest among people regarding the potential of natural plants in treating the infections and disorders of oral cavity. In conclusion it can be revealed that the crude ethanolic extract of Spilanthes leaves possess significant antinociceptive as well as antioxidant activities. The potential of the extract of Spilanthes as antinociceptive and antioxidant agents may be due to the presence of phytoconstituents like tannins, flavonoids, phenolics etc that might be responsible for its activity and justify its use as a traditional folk remedy for toothache. However, extensive research is necessary to search for active principles responsible for these activities. To add, clinical trials are warranted to justify the ancient and pre-clinical findings about medicinal applications of Spilanthes herbal agents in oral hygiene.

ACKNOWLEDGEMENT

Authors are thankful to Kemwell Biopharma Pvt Ltd., Bangalore for their encouragement for this study.

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Source of support: Nil, Conflict of interest: None Declared