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______Review Article

A REVIEW ON PHARMACOLOGICAL USES AND MECHANISM OF ACTION OF BILIMBI LINN. Jasmine Shalet D Souza1*, Karunakar Hegde2 and AR Shabaraya2 1 Rajiv Gandhi University of Health Sciences, Bangalore, , . 2 Department of Pharmacolgy, Srinivas College of Pharmacy, Valachil, Farangipete post, Managalore – 574143, Karnataka, India. ______ABSTRACT , commonly known as bilimbi, is a fruit bearing tree of Averrhoa and family . The fruit, flower and leaves are used in folk medicines for various indications like obesity, hyperlipidemea, diabetes, etc. It’s rich various phytoconstituents like saponins, flavonoids, terpenoids etc. It is proved to have various pharmacological actions like antidiabetic, antioxidant, antimicrobial etc. The prime objective of this review is to accumulate and organize articles on Averrhoa bilimbi and its proved pharmacological action and its mechanism of action.

Key Words: Bilimbi, Averrhoa bilimbi, pharmacological uses, mechanism of action.

INTRODUCTION Averrhoa bilimbi leaves contain aldehyde, Herbal medication had been practiced long sugar and protein and secondary metabolites before recorded history. Herbal medicines are like cardiac glycoside, flavanoid ,alkaloid , considered relatively safe with no side phenol , tannin and coumarin while effects1.One such with wide range of carbohydrate, starch, ketose, fat, amino acid, uses is Averrhoa bilimbi. Its leaves and fruits acid and resins were absent in leaves5. were used traditionally for various indications, in the form of decoction, infusion, fruit juice MINERAL CONTENT etc.2 Averrhoa bilimbi (Bilimbi) is medicinally Mature fruits of Averrhoa bilimbi have used as a folk remedy for many symptoms. It potassium and phosphorus in highest quantity is used as antibacterial, antiscorbutic, and also traces of sodium, magnesium, astringent; post–partum protective medicine. It calcium, zinc, manganese and ferric ions6. is also used for the treatment of fever, mumps, pimples, inflammation of the rectum and VOLATILE COMPONENTS diabetes, itches, boils, rheumatism, syphilis, About Fifty-three volatile components are bilious colic, whooping cough, hypertension, present in Averrhoa bilimbi, among which and stomach ache. aliphatic acids are present highest quantity7.

Family: Oxedacae Kingdom: Plantae

PHYTOCONSTITUENTS Averrhoa bilimbi fruits are rich in flavonoids. Saponins, phenols, coumarins. LC-MS showed the presence of about twenty compounds in the fruits. They are Trans-resveratrol, Umbelliferone, Salicylic acid, Methyl salicylate, Dihydro myrecetin, Eriocitrin, Boswellic acid, Hydroxy aristolochic acid, Cinnnamaldehyde, Benzyl cinnamate, Hydroxy-citric acid lactone, Benzyl alcohol, Phenyethyll amine, Leaf Alcohol, Caffeolmalic acid, Citric acid, Tartaric acid, Ascorbic acid, Xylose, Tyrosine4.

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ANTIOXIDANT ACTIVITY Antioxidants are the substances which inhibit oxidation. Oxidation is a chemical reaction that can produce free radicals, thereby leading to chain reactions that may damage the cells of organisms. Methanolic extract of Averrhoa bilimbi showed a good dose dependent DPHH scavenging activity13. The antioxidants property of Averrhoa bilimbi is also proved in a invivo study done in paracetamol intoxicated Wister rats. The antioxidant activity was elucidated by determining the Superoxide dismutase (SOD), Glutathione, Glutathione peroxidise (GPx) levels14. Mechanism of action Averrhoa bilimbi is rich in phenolics compounds such as phenolic acid flavonoids tannins which play a major role in its antioxidant activity15.

ANTICANCER ACTIVITY S. Jaghadeesh et al. studied the anti lymphoma activity of Averrhoa bilimbi fruit extract on Swiss albino mice. The analysis of haematological parameter and MTT assay proved its anticancer activity. There was a PHARMACOLOGICAL USES significant reduction in body weight and ANTIMICROBIAL ACIVITY tumour volume as well as up to 97% inhibition In a study done by Z A Zakaria at al. it was of cell growth in MTT assay16. The ethanolic proved that the Averrhoa bilimbi has potent leaves extract also have a potent anticancer antimicrobial activity. Both the leaves as well activity. The anticancer activity of fruit and as the fruits were lethal to wide range of leaves is proved true for human breast cancer microorganisms. They also compared the cell lines also. Fruits are more cytotoxic than antimicrobial activity of aqueous and the leaves17. chloroform extract and aqueous extract was Mechanism of action found to be active against Gram positive Averrhoa bilimbi is rich in phenols, flavonoids, microorganisms like S. aureus, S. epidermis B. terpenoids, saponins, and steroids. And it is cereus, C. diphteriae, while the chloroform also a good antioxidant agent.13These extract showed potent activity against Gram- compounds play a major role in cancer positive bacterias like S. aureus, S. epidermis, through their effects on signal transduction in B. cereus, K. rhizophila and C. diphteriae. Both cell proliferation and angiogenesis 18. the extracts showed good activity against 8 Gram negative bacteria as well. In another ANTIDIABETIC ACTIVITY comparison study done by Md. Abdullah Aziz Averrhoa bilimbi is very effective in normalizing et.al. , water extract of Averrhoa bilimbi leaves the elevated blood glucose level. The same is extract was found to have good antimicrobial proved in streptozocin induced diabetic rats. property compared to the ethanol and 9 Administration of Averrhoa bilimbi leaf extract methanol extract of the same . Seri Intan reduced the elevated blood glucose level by Mokhtar et al studied the antimicrobial property 50%. Reactive free radicals may be generated of Averrhoa bilimbi at different maturity stages as a result of hyperglycaemia induced by the and concluded that the young and mature streptozocin, which may lead to peroxidation of stages of the fruits has more potent activity lipids. This may ultimately result in increase in against bacteria than the ripe fruits10. the levels of TxA2 and TxB2 and thus platelet Mechanism of action aggregation. Averrhoa bilimbi prevents the Averrhoa bilimbi is rich in a number of platelet aggregation by formation of TBARS phytochemical constituents. The presence of (thiobarbituric acid reactive substances strong acid such as oxalic acid makes it a 11 (TBARS) Thus it has a hypoglycaemic, potent antimicrobial agent. . Also the hypotriglyceridemic, antiatherogenic, antilipid presence of surplus phytochemical is the peroxidation property in streptozocin induced reason for the antibacterial effects exhibited by the extracts 12.

International Journal of Pharma And Chemical Research I Volume 5 I Issue 2 I Apr – Jun I 2019 ISSN 2395-3411 Available online at www.ijpacr.com 102 diabetic rats19. The Averrhoa bilimbi fruits also ANTHELMINTIC PROPERTY processes good antidiabetic activity20. Methanolic extract of Averrhoa bilimbi has a Mechanism of action19 very good anthelmintic property. The same is It is believed to have similar mechanism action proved in earthworm which has similar as metformin. So it acts by physiological and anatomical property as that  Increasing glucose utilization of intestinal worms. Methanolic extract of  Increasing the expression of insulin Averrhoa bilimbi paralysed and then killed the receptors worms in a period less than that of the  By reducing hepatic gluconeogenesis standard drug that is albendazole. Mechanism by which it acts as anthelmintic agent is 24 HEPATOPROTECTIVE ACTIVITY21 unknown . Methanolic extract of Averrhoa bilimbi also found to have hepatoprotective activity. ANTIMALARIAL ACTIVITY Averrhoa bilimbi showed its hepatoprotective Methanolic extract of Averrhoa bilimbi leaves activity by lowering the increased serum has been proved for its antimalarial action. It marker enzyme and lipid peroxide levels in showed a dose dependent inhibition of CCL4 intoxicated rats. It showed a dose parasite plasmodium faciparum invitro. For this dependent action. cultured plasmodium faciparum were used Mechanism of action which were incubated with human serum for CCl4 forms free radical which in turn results in blood smear preparation. It is considered to membrane damage, increase in serum have a good antimalarial activity since the enzymes such as SGOT SGPT etc. It also IC50 value was less than 10µg/ml. It showed a results in decrease in antioxidant system such good activity at a concentration as low as as glutathione (GSH) and hypoabuminemia as 2.805µg/ml with action increasing with well as hyperbilirubinemia. Averrhoa bilimbi concentration. has a good antioxidant property. Administration Mechanism of action of methanolic extract of Averrhoa bilimbi The antimalarial property of Averrhoa bilimbi is resulted in increase in antioxidant levels such due to the presence of a flavonoids- Luteolin as GSH, which in turn reversed the free radical which is soluble in methanol. It acts on the Fab mediated effects. 1 enzyme and inhibits it, resulting in the inhibition of fatty acid chain extension cycle. CARDIOVASCULAR DISEASES This results in the inhibition of growth of P. 25 A study is conducted to study the cardiac falciparum . contractility and heart rate by Anne Caroline et al. in guinea pigs. And it is found that Averrhoa DENTAL BLEACHING AGENT bilimbi reduces the heart rate and atrial Bleaching refers to restoration of a natural contractility22.Averrhoa bilimbi also has a good tooth shade. They are used in case of teeth anticoagulant property. It didn’t show an discoloration hydrogen peroxide and immediate action after intake of Averrhoa carbamide peroxide are bleaching agents most bilimbi as it takes some time to get activated. It often used. The bleaching property of is predicted that in future it may be useful in Averrhoa bilimbi is proved invitro by Cut reducing stroke, heart attack, venous Fauziah et al. Both qualitative and quantitative thrombosis and other cardiovascular diseases. data suggested that the Averrhoa bilimbi has It can also be used in surgeries to reduce clot potential to change the colour of enamel, but formation23. the result obtained was less than standard

Mechanism of action chemical bleaching agent carbamide peroxide 26 The exact mechanism by which Averrhoa . bilimbi reduces clot formation is unknown. But Further studies are conducted by I M Msandi it is assumed that presence of high level of et al. to test enamel colour change effect of oxalic acid makes it a good anticoagulant extract of Averrhoa bilimbi fruit in the form of agent. Since it is metallic ion chelator it might gel. The study was done in bovine incisive act by interfering with the action of calcium or teeth. It proved that application Averrhoa sodium mediated thrombin activation. Binding bilimbi extract gel which was prepared using to calcium ions results in prevention of the carboxymethyl cellulose at different polymerization of fibrin and inactivation of concentration resulted in discoloration of teeth 27 sodium ions inhibits the subsequent thrombin to brownish yellow colour . activation23. Mechanism of action The presence of peroxide and acid is believed to be the reason for tooth whitening property of Averrhoa bilimbi.

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ULCERATIVE COLITIS28 the activity. Further the active constituents Ulcerative colitis is an inflammatory bowel were isolated using various solvents from the disease that causes long lasting inflammation soluble portion of alcohol precipitate of the and ulcers. Ulcerative colitis affects the water fruit extract. In that, ethyl acetate fraction innermost lining of the colon and rectum. The gave a good result at a lower concentration effect of Averrhoa bilimbi fruit extract on compared to butanol and aqueous fraction. All ulcerative colitis was studied using Wister of these parts showed a decrease in albino rats. There was a decrease in mucosal cholesterol levels like LDL, TG and total ulcers and inflammatory mediators level in cholesterol and increase in good cholesterol Averrhoa bilimbi treated rats compared to HDL. control. Mechanism of action Mechanism of action Averrhoa bilimbi has flavonoids, tannins, Averrhoa bilimbi is a very good antioxidant terpenoids and phenols. The synergistic action agent which is believed to be the reason of theses constituent might be the reason for behind the protective effect against ulcerative antihyperlipidemia. colitis. NO level decreased while SOD and GSH level was found to be increased in colon OXIDATIVE STRESS33 region. Ethyl acetate extract of Averrhoa bilimbi is effective in reducing oxidative stress due to GINGIVAL WOUND HEALING PROPERTY29 diabetes. The same is proved by estimation of Gingival wound healing is an important serum glucose, glycated haemoglobin, plasma process as it prevents the further microbial insulin, hydroperoxides. Even the infection. Increase in fibroblast level is histopathology of lever also showed protective considered as an index of wound healing. It effect against oxidative damage. showed a dose dependent action with highest Mechanism of action activity at a concentration from 10 to 20%., Presence of Quercetin might be the reason while the action decreased at higher behind its protective effect against oxidative concentration. stress. Mechanism of action Immediately after tissue injury various OTHER USES pathways get activated and synchronized to RIPENING OF FRUITS34 prevent infection. The cells involved in wound Masilungan, G.D et al. proved the ripening healing include immune system cell such effect of Averrhoa bilimbi in Saba banana. monocytes, lymphocytes, endothelial cells, Presence of bilimbi fruit hastened the ripening keratinocytes and fibroblasts. These cells of the banana compared to control. While undergo massive fluctuations in gene injured bilimbi fruit further hastened the expression, resulting in important changes in ripening. Averrhoa bilimbi produces Ethylene cell proliferation, differentiation and migration. which accounts for its ripening activity. After Averrhoa bilimbi administration there was more increase in fibroblast level compared to TOXICITY35 control indicating the wound healing property Intake of highly concentrated Averrhoa bilimbi of Averrhoa bilimbi. fruit juice results in renal injury. This is due to the high oxalate content of the fruits. HYPOLIPIDEMIC ACTIVITY30, 31, 32 Flower, fruit as well as fruit extract of Averrhoa CONCLUSION bilimbi has hypolipidemic activity. 400mg/kg of The presence of various constituents like leaves extract of Averrhoa bilimbi showed a saponins, terpenoids, flavonoids, quercetin etc response similar to, and in some parameter contribute to the various pharmacological better response than standard drug in action of Averrhoa bilimbi. Studies have been streptozocin induced diabetic rats. The done on fruits, leaves as well as flowers of hypolipidemic activity of Averrhoa bilimbi bilimbi. It is a very good anti diabetic, flowers has also proved in-vitro. In case of Antihyperlipidemic, antimicrobial, fruits only the fruit and water extract of fruit hepatoprotective, anthelmintic, antioxidant, showed to have activity, while alcohol and agent. Further it is found to be useful in hexane extract did not show any hypolipidemic malaria, gingival wound healing etc. Further activity. The action showed by fruit is detailed studies are required to elucidate its independent of dose at 125mg/kg and beneficiary effect on various diseases. But 250mg/kg while water extract showed an administration of higher concentration of increase in activity from 25 to 50mg/kg but Averrhoa bilimbi fruit for a prolonged period of further increase in dose resulted in decline in time is injurious to kidney.

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