Anti-diabetic Activity of Partially Purified Santalin A from the Heartwood of Pterocarpus santalinus L.f. in Alloxan-induced Diabetic Wistar Rat
Authors
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Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Hyderabad − 500046, Telangana ,IN
Jyothi Chaitanya Pagadala -
Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad − 500046, Telangana ,INSuresh Yenugu
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Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Hyderabad − 500046, Telangana ,INPadmaja Gudipalli
DOI:
https://doi.org/10.18311/jer/2021/28024Keywords:
Antidiabetic, Antioxidant, Oxidative Stress, Red Sanders, SantalinsAbstract
The ever-increasing use of plant-based pharmaceuticals as alternatives to conventional drugs for disease management demands identification, isolation, and characterization of novel compounds. Despite the potential of plant extracts to mitigate the morbidity of diseases, several active principles are preferred to avoid the interference of other compounds. The promising health benefits of the extracts and isolated compounds of Pterocarpus santalinus in the treatment of diabetes, cardiovascular disease, cancer, and infections have been described. However, such studies on the active principle, namely, santalins, are not reported. In this study, we standardized the isolation of a mixture of santalins A and B from the heartwood of P. santalinus by column chromatography followed by preparative TLC and HPLC. The partially purified santalins were characterized by LC-MS, HR-MS, and 1H NMR analyses. The isolated combination of santalins displayed higher total antioxidant and DPPH free radical scavenging activity in vitro than the crude heartwood extracts. Administration of the mixture of santalins A and B did not exhibit any antihyperglycemic activity in the liver, kidney, and pancreas of alloxan-induced diabetic rats. However, pretreatment of rats with a mixture of santalins at a dose of 1.0 mg/kg body weight prevented alloxan-induced diabetes as indicated by the normal blood glucose levels. Hyperglycemia-associated lipid peroxidation was abrogated in santalin-pretreated rats that did not develop alloxan-induced diabetes. Furthermore, the alterations in catalase, glutathione peroxidase, and glutathione-S-transferase activities in the pancreas of santalinpretreated rats could be responsible for preventing damage to the pancreas and thus non-induction of diabetes following alloxan treatment. Therefore, for the first time, we report the simplified procedure for isolating a mixture of santalins, including their ability to prevent the induction of diabetes in Wistar rats. The outcome of our study has significant clinical importance to the fact that supplementation of santalins may potentially avoid or delay the onset of diabetes in high-risk individuals.
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Pandey MM, Rastogi S, Rawat AKS. Indian traditional ayurvedic system of medicine and nutritional supplementation. eCAM. 2013; 2013(376327):1-12. https://doi.org/10.1155/2013/376327. PMid:23864888 PMCid:PMC3705899.
Salmeron E, Garrido-Cardenas JA, Manzano-Agugliaro F. Worldwide research trends on medicinal plants. Int J Environ Res Public Health. 2020; 17(10):2-20. https://doi.org/10.3390/ijerph17103376. PMid:32408690 PMCid: PMC7277765.
Vasisht K, Sharma N, Karan M. Current perspective in the international trade of medicinal plants material: An update. Curr Pharm Des. 2016; 22(27):4288-336. https://doi.org/10.2174/1381612822666160607070736. PMid:27281331.
Unuofin JO, Lebelo SL. Antioxidant effects and mechanisms of medicinal plants and their bioactive compounds for the prevention and treatment of type 2 diabetes: An updated review. Oxid Med Cell Longev. 2020; 2020(1356893):1-36. https://doi.org/10.1155/2020/4205640. PMid:32802265 PMCid:PMC7415084.
Akram M, Riaz M, Munir N, et al. Progress and prospects in the management of bacterial infections and developments in phytotherapeutic modalities. Clin Exp Pharmacol Physiol. 2020; 47(7):1107-1119. https://doi.org/10.1111/1440-1681.13282. PMid:32064656.
Ben-Shabat S, Yarmolinsky L, Porat D, Dahan A. Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies. Drug Deliv Transl Res. 2020; 10(2):354-367. https://doi.org/10.1007/s13346-019-00691-6. PMid:31788762 PMCid:PMC7097340.
Ahmad R, Khan MA, Srivastava AN, et al. Anticancer potential of dietary natural products: A comprehensive review. Anticancer Agents Med Chem. 2020; 20(2):122-236. https://doi.org/10.2174/187152061966619101510371 2. PMid:31749433.
Chukwuma CI, Matsabisa MG, Ibrahim MA, et al. Medicinal plants with concomitant anti-diabetic and antihypertensive effects as potential sources of dual-acting therapies against diabetes and hypertension: A review. J Ethnopharmacol. 2019; 10(235):329-360. https://doi.org/10.3917/telev.010.0235.
Hughes K, Ho R, Butaud JF, et al. A selection of eleven plants used as traditional Polynesian cosmetics and their development potential as anti-aging ingredients, hair growth promoters, and whitening products. J Ethnopharmacol. 2019; 245:112-159. https://doi.org/10.1016/j.fertnstert.2019.04.035. PMid:31200967.
Medellin-Luna MF, Castaneda-Delgado JE, Martinez- Balderas VY, Cervantes-Villagrana AR. Medicinal plant extracts and their use as wound closure inducing agents. J Med Food. 2019; 22(5):435-443. https://doi.org/10.1089/jmf.2018.0145. PMid:30942656.
Hunt KA, Fate J, Dodds B. Cultural and social influences on the perception of beauty: A case analysis of the cosmetics industry. Journal of Business Case Studies. 2011; 7(1):1-10. https://doi.org/10.19030/jbcs.v7i1.1577.
Ribechini E, Modugno F, Perez-Arantegui J, Colombini MP. Discovering the composition of ancient cosmetics and remedies: analytical techniques and materials. Anal Bioanal Chem. 2011; 401(6):1727-1738. https://doi.org/10.1007/s00216-011-5112-2. PMid:21637932.
Bulle S, Reddyvari H, Nallanchakravarthula V, Vaddi DR. Therapeutic potential of Pterocarpus santalinus L.: An update. Pharmacogn Rev. 2016; 10(19):43-49. https://doi.org/10.4103/0973-7847.176575. PMid:27041873 PMCid: PMC4791987.
Aruna Kumara KKIU, Walpola BC, Subasinghe S, Yoon MH. Pterocarpus santalinus Linn. f. (Rathhandun): A review of its botany, uses, phytochemistry and pharmacology. J Korean Soc Appl Biol Chem. 2011; 54(4):495-500.
Narayan S, Devi RS, Srinivasan P, Shyamala Devi CS. Pterocarpus santalinus: a traditional herbal drug as a protectant against ibuprofen induced gastric ulcers. Phytother Res. 2005; 19(11):958-962. https://doi.org/10.1002/ptr.1764. PMid:16317653.
Navada KK, Vittal RR. Ethanomedicinal value of Pterocarpus santalinus (Linn.f.), a Fabaceace member. Orient Pharm Exp Med. 2014; 14(4):313-317. https://doi.org/10.1007/s13596-014-0168-0.
Manjunatha BK. Antibacterial activity of Pterocarpus santalinus. Indian J Pharm Sci. 2006; 68(1):115-116. https://doi.org/10.4103/0250-474X.22982.
Kumar D. Anti-inflammatory, analgesic, and antioxidant activities of methanolic wood extract of Pterocarpus santalinus L. J Pharmacol Pharmacother. 2011; 2(3):200- 202. https://doi.org/10.4103/0976-500X.83293. PMid: 21897722 PMCid:PMC3157138.
Jaywant J, Ghanshyam G, Aruna K. Angiogenic effects of Pterocarpus santalinus in the chick chorioallantoic membrane. Drug Invention Today. 2011; 3(6):62-68.
Stella J, Krishnamoorthy P, Mohamed AJ, Anand M. Free radical scavenging and antibacterial evaluation of Pterocarpus santalinus leaf in vitro study. Int J Pharma Sci Res. 2011; 2(5):1204-1208.
Kondeti VK, Badri KR, Maddirala DR, et al. Effect of Pterocarpus santalinus bark, on blood glucose, serum lipids, plasma insulin, and hepatic carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats. Food Chem Toxicol. 2010; 48(5):1281-1287. https://doi.org/10.1016/j.fct.2010.02.023. PMid:20178824.
Tennakone K, Kumara GRRA, Kottegoda IRM, et al. Sensitization of nano-porous films of TiO2 with santalin (red sandalwood pigment) and construction of dyesensitized solid-state photovoltaic cells. J Photochem Photobiol A: Chemistry. 1998; 117(8):137-142. https://doi.org/10.1016/S1010-6030(98)00344-X.
Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem. 1999; 269(2):337-341. https://doi.org/10.1006/abio.1999.4019. PMid:10222007.
Arokiyaraj S, Martin S, Kantharaj P, et al. Free radical scavenging activity and HPTLC fingerprint of Pterocarpus santalinus L. - An in vitro study. Ind J Sci Technol. 2008; 1(7):1-3. https://doi.org/10.17485/ijst/2008/v1i7.3, https://doi.org/10.17485/ijst/2008/v1i6.8.
Suresh Y, Das UN. Differential effects of saturated, monounsaturated, and polyunsaturated fatty acids on alloxan-induced diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 2006; 74(3):199-213. https://doi.org/10.1016/j.plefa.2005.11.006. PMid:16412622.
Bernheim F. The oxidative desulfuration of thio-acids. Biochim Biophys Acta. 1964; 19(90):426-428. https://doi.org/10.1016/0304-4165(64)90216-8.
Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967; 70(1):158-169.
Jakoby WB. The glutathione S-transferases: A group of multifunctional detoxification proteins. Adv Enzymol Relat Areas Mol Biol. 1978; 46:383-414. https://doi.org/10.1002/9780470122914.ch6. PMid:345769.
Aebi H. Catalase in vitro. Methods Enzymol. 1984; 105:121- 126. https://doi.org/10.1016/S0076-6879(84)05016-3.
Caesar LK, Cech NB. Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Nat Prod Rep. 2019; 36(6):869-888. https://doi.org/10.1039/C9NP00011A. PMid:31187844 PMCid:PMC6820002.
Jung K, Jeon J, Ahn M, et al.. Preparative isolation and purification of flavonoids from Pterocarpus santalinus using centrifugal partition chromatography. J Liq Chrom Relat Tech. 2012; 35(17):2462-2470. https://doi.org/10.1080/10826076.2011.633680.
Azamthulla M, Anbu J, Babu VLA, Rajkapoor B. Isolation and characterization of Pterocarpus santalinus heartwood extract. Der Pharmacia Lettre. 2016; 8(12):34-39.
Yeole PG, Wadher SJ, Gaikwad NJ. Free radical scavenging activity of water extract of heartwood of Pterocarpus marsupium. J Nat Remedies. 2008; 8(1):89-92.
Gupta P, Jain V, Pareek A, et al. Evaluation of the effect of alcoholic extract of heartwood of Pterocarpus marsupium on in vitro antioxidant, anti-glycation, sorbitol accumulation, and inhibition of aldose reductase activity. J Tradit Complement Med. 2016; 7(3):307-314. https://doi.org/10.1016/j.jtcme.2016.11.001. PMid:28725625 PMCid: PMC5506622.
Pradhan S, Sahu SK, Panda S, et al. Hypoglycaemic effect of Pterocarpus marsupium. J Anat Soc India. 2017; 66:S42. https://doi.org/10.1016/j.jasi.2017.08.135.
Mishra A, Srivastava R, Srivastava SP, et al. Antidiabetic activity of heartwood of Pterocarpus marsupium Roxb. and analysis of phytoconstituents. Indian J Exp Biol. 2013; 51(5):363-374.
Gairola S, Gupta V, Singh B, et al. Phytochemistry and pharmacological activities of Pterocarpus marsupium- A Review. Int Res J Pharm. 2010; 1(1):100-104.
Mohankumar SK, Shea TO, McFarlane JR. Insulinotropic and insulin-like effects of a high molecular weight aqueous extract of Pterocarpus marsupium Roxb. hardwood. J Ethnopharmacol. 2012; 141(1):72-79. https://doi.org/10.1016/j.jep.2012.02.002. PMid:22343091.
Dhanabal SP, Kokate CK, Ramanathan M, et al. Hypoglycaemic activity of Pterocarpus marsupium Roxb. Phytother Res. 2006; 20(1):4-8. https://doi.org/10.1002/ ptr.1819. PMid:16397913.
Mukhtar HM, Ansari SH, Ali M, et al. Effect of aqueous extract of Pterocarpus marsupium wood on alloxaninduced diabetic rats. Pharmazie. 2005; 60(6):478-479.
Vats V, Grover JK, Rathi SS. Evaluation of antihyperglycemic and hypoglycemic effect of Trigonella foenum-graecum Linn., Ocimum sanctum Linn. and Pterocarpus marsupium Linn. in normal and alloxanized diabetic rats. J Ethnopharmacol. 2002; 79(1):95-100. https://doi.org/10.1016/S0378-8741(01)00374-9.
Ahmad F, Khalid P, Khan MM, et al. Hypoglycemic activity of Pterocarpus marsupium wood. J Ethnopharmacol. 1991; 35(1):71-75. https://doi.org/10.1016/0378- 8741(91)90134-Y.
Patidar A, Tonpay SD, Agrawal N. Hypoglycemic activity of Pterocarpus marsupium in patients with Type 2 diabetes mellitus. Int J Basic Clin Pharmacol. 2015; (6)4:1189-1193. https://doi.org/10.18203/2319-2003.ijbcp20151356.
Halim MA, Mishra A. The effects of the aqueous extract of Pterocarpus santalinus heartwood and vitamin E supplementation in streptozotocin-induced diabetic rats. J Med Plants Res. 2011; 5(3):398-409.
Kameswara Rao B, Giri R, Kesavulu MM, Apparao C. Treatment of diabetes mellitus: plant drugs vs. oral hypoglycaemic agents and insulin. In: Govil, JN, Khalil Ahmad VKS (Ed). Recent Progress in Medicinal Plants. Vol. 14. Biopharmaceuticals LLC, Studium Press, Texas, USA; 2006. p. 279-296.
Kameswara Rao B, Giri R, Kesavulu MM, Apparao C. Effect of oral administration of bark extracts of Pterocarpus santalinus L. on blood glucose level in experimental animals. J Ethnopharmacol. 2001; 74(1):69-74. https://doi.org/10.1016/S0378-8741(00)00344-5.
Singh PK, Baxi D, Banerjee S, Ramachandran AV. Therapy with methanolic extract of Pterocarpus marsupium Roxb. and Ocimum sanctum Linn. reverses dyslipidemia and oxidative stress in alloxan induced type I diabetic rat model. Exp Toxicol Pathol. 2012; 64(5):441-448. https://doi.org/10.1016/j.etp.2010.10.011. PMid:21106356.
Gupta R, Gupta RS. Effect of Pterocarpus marsupium on streptozotocin-induced oxidative stress in kidney of diabetic Wistar rats. J Herbs Spices Med Plants. 2011; 17(2):169-182. https://doi.org/10.1080/10496475.2011.584 291.
Gayathri M, Kannibaran K. Studies on the ameliorative potential of aqueous extract of bark of Pterocarpus marsupium Roxb. in streptozotocin-induced diabetic rats. J Nat Remedies. 2010; 10(1):36-43.
Badawy REEl, Ibrahim KA, Hassan NS, Sayed WMEl. Pterocarpus santalinus ameliorates streptozotocin-induced diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function. Iran J Basic Med Sci. 2019; 22(8):932-939.
