CITRONELLOL: A POTENTIAL ANTIOXIDANT AND ALDOSE REDUCTASE INHIBITOR FROM CYMBOPOGON CITRATUS
Keywords:
Diabetes mellitus, Aldose reductase inhibition, Citronellol, Antioxidant activity, Molecular dockingAbstract
Objective: The present study deals with identification of bioactive component from the distillate of Cymbopogon citratus plant and to evaluate its aldose reductase inhibitory and antioxidant activity.
Methods: The aldose reductase enzyme was semi purified by ammonium sulphate precipitation from chicken eye lens. Differential solvent extraction of Cymbopogon citratus was carried out and by using HPLC, HPTLC and Gas chromatography active component responsible for aldose reductase inhibition was identified. The Oral Glucose Tolerance Test was carried by induction of diabetes to the male Wistar rats with streptozotocin. The sorbitol content was measured by sorbitol dehydrogenase enzyme. The antioxidant activity was studied using DPPH and FRAP methods.
Results: Differential solvent extraction of the distillate revealed presence of aldose reductase inhibitory activity in the petroleum ether extract of the plant. Citronellol was identified as bioactive component by HPLC, HPTLC and gas chromatography. Citronellol demonstrated 90.4% inhibition of aldose reductase with an IC50 value of 19.6 ±0.8 µg/ ml as against 92.3 % inhibition by the standard drug epalrestat with an IC50 value 9.8 ±0.43 µg/ ml. It demonstrated better lowering of sorbitol (44%) than epalrestat (28%) in the eye lens studies as compared to the diabetic control. Kinetic studies using Lineweaver Burk Plot revealed citronellol to be a mixed type of inhibitor. Docking studies revealed the binding of citronellol at a site similar to epalrestat.
Conclusion: Citronellol from C. citratus is found to possess potent aldose reductase inhibitory activity with mixed type of enzyme inhibition and a very good antioxidant potential.
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Brock C, Softeland E, Frokjaer JB, Drewes AM, Nielsen LA. Associations between sensorimotor, autonomic and central neuropathies in diabetes mellitus. J Diabetes Metab 2014;5:1-6.
International diabetes federation. IDF diabetes atlas, 6th ed. Brussels, Belgium; 2013.
Reddy GB, Satyanarayana A, Balakrishna N, Ayyagari R, Padma M, Viswanath K, et al. Erythrocyte aldose reductase activity and sorbitol levels in diabetic retinopathy. Mol Vis 2008;14:593-601.
Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Banting Lecture Diabetes 2005;54:1615-25.
Kato A, Yasuko H, Goto H, Hollinshead J, Nash RJ, Adachi I. Inhibitory effect of rhetsinine isolated from Evodia rutaecarpa on aldose reductase activity. Phytomed 2009;16:258-61.
Kador PF, Kinoshita JH, Sharpless NE. Aldose reductase inhibitors: a potential new class of agents for the pharmacological control of certain diabetic complications. J Med Chem 1985;28:841-9.
Suryanarayana P, Kumar PA, Saraswat M, Petrash JM, Reddy GB. Inhibition of aldose reductase by tannoid principles of Emblica officinalis: implications for the prevention of sugar cataract. Mol Vis 2004;10:148-54.
Singi G, Damasceno DD, D’Andrea ED, Silva GA. Acute effects of Allium sativum L. and Cymbopogon citratus (DC) Stapf. hydroalcoholic extracts on arterial blood pressure of anesthetized rats. Braz J Pharmacogn 2005;15:94-7.
Viana GS, Vale TG, Pinho RS, Matos FJ. Antinociceptive effect of the essential oil from Cymbopogon citratus in mice. J Ethnopharmacol 2000;70:323-7.
Quintans-Júnior LJ, Souza TT, Leite BS, Lessa NM, Bonjardim LR, Santos MR, et al. Phythochemical screening and anticonvulsant activity of Cymbopogon winterianus Jowitt (Poaceae) leaf essential oil in rodents. Phytomed 2008;15:619-24.
Tzortzakis NG, Economakis CD. Antifungal activity of lemongrass (Cymbopogon citratus L.) essential oil against key postharvest pathogen. Innov Food Sci Emerg Technol 2007;8:253–8.
Silva MR, Ximenes RM, da Costa JG, Leal LK, de Lopes AA, Viana GS. Comparative anticonvulsant activities of the essential oils (EOs) from Cymbopogon winterianus Jowitt and Cymbopogon citratus (DC) Stapf. in mice. Naunyn Schmiedebergs Arch Pharmacol 2010;381:415–26.
Menut C, Bessiére JM, Samaté D, Djibo AK, Buchbauer G, Schopper B. Aromatic plants of tropical west africa. XI. Chemical composition, antioxidant and antiradical properties of the essential oils of three Cymbopogon species from Burkina Faso. J Essent Oil Res 2000;12:207-12.
Wiernsperger NF. Oxidative stress as a therapeutic target in diabetes: revisiting the controversy. Diabetes Metab 2003;29:579-85.
Sarges R, Oates PJ. Aldose reductase inhibitors: recent developments. Prog Drug Res 1993;40:99-161.
Kador PF, Sharpless NE. Pharmacophor requirements of aldose reductase inhibitor site. Mol Pharmacol 1983;24:521-31.
Rastelli G, Ferrari AM, Costantino L, Gamberini MC. Discovery of new inhibitors of aldose reductase from molecular docking and database screening. Bioor Med Chem 2002;10:1437-50.
Hayman S, Kinoshita JH. Isolation and properties of lens aldose reductase. J Biol Chem 1965;240:877-82.
Gacche RN, Dhole NA. Profile of aldose reductase inhibition, anti-cataract and free radical scavenging activity of selected medicinal plants: an attempt to standardize the botanicals for amelioration of diabetes complications. Food Chem Toxicol 2011;49:1806-13.
Dongare V, Kulkarni C, Kondawar M, Magdum C, Haldavnekar V, Arvindekar AU. Inhibition of aldose reductase and anti-cataract action of trans-anethole isolated from Foeniculum vulgare Mill. Fruits Food Chem 2012;135:385-90.
Kumar MS, Reddy PY, Kumar PA, Surolia I, Reddy GB. Effect of dicarbonyls induced browning on alpha-crystallin chaperone-like activity: physiological significance and caveats of in vitro aggregation assays. Biochem J 2004;379:273–82.
Hye-LN, Yunying H, Tae-SP, Thomas D, Andrew JN, Kazue O, et al. Regulation of plasma fructose and mortality in mice by the aldose reductase inhibitor lidorestat. J Pharmacol Exp Ther 2009;328:496–503.
Patil SB, Ghadyale VA, Taklikar SS, Kulkarni CR, Arvindekar AU. Insulin secretagogue, alpha-glucosidase and antioxidant activity of some selected spices in streptozotocin-induced diabetic rats. Plant Foods Hum Nutr 2011;66:85-90.
Andrade-Cetto A, MartÃnez-Zurita E, Wiedenfeld H. Hypoglycemic effect of Malmea depressa root on streptozotocin diabetic rats. J Ethnopharmacol 2005;100:319-22.
Pari L, Suresh A. Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats. Food Chem Toxicol 2008;46:1627-34.
Panaskar SN, Joglekar MM, Taklikar SS, Haldavnekar VS, Arvindekar AU. Aegle marmelos Correa leaf extract prevents secondary complications in streptozotocin-induced diabetic rats and demonstration of limonene as a potent antiglycating agent. J Pharm Pharmacol 2013;65:884-94.
Umamaheswari M, Aji CS, Kuppusamy A, Thirumalaisamy S, Varadharajan S, Puliyath J, et al. In Silico docking studies of aldose reductase inhibitory activity of selected flavonoids. Int J Drug Dev Res 2012;4:328-34.
Legacy tobacco documents library, Burdock group, Toxicology and risk assessment. University of California, San Francisco; 2003.
Ramana KV. Aldose reductase: new insights for an old enzyme. Biomol Concepts 2011;2:103-14.
Adeneye AA, Agbaje EO. Hypoglycemic and hypolipidemic effects of fresh leaf aqueous extract of Cymbopogon citratus Stapf in rats. J Ethnopharmacol 2007;112:440-4.
Urzhumtsev A, Tete-Favier F, Mitschler A, Barbanton J, Barth P, Urzhumtseva L, et al. A ‘specificity’ pocket inferred from the crystal structures of the complexes of aldose reductase with the pharmaceutically important inhibitors tolrestat and sorbinil. Struct 1997;5:601-12.