Vitis Elegan as a Promising Antidiabetic Herb: Phytochemical and Pharmacological Assessment


1 Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia

3 Research Center for Molecular and Cellular Imaging, Tehran University of Medical sciences, Tehran, Iran

4 Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran

5 Department of Surgical Oncology, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran

6 Department of Genetic, Central Tehran Branch, Islamic Azad University, Tehran, Iran

7 Young Researchers and Elite Club, East Tehran Branch, Islamic Azad University, Tehran, Iran


In this research, we investigated the antidiabetic activity of Vitis elegans rhizome, which is used as traditional treatment for diabetes mellitus. The methanol, chloroform, petroleum ether, and hexane extracts of the plant root were obtained through serial exhaustive extraction and were analyzed by Thin Layer Chromatography (TLC).  Glycogen phosphorylase (GP) assay was done to determine the inhibitory effects of respective extracts on GP enzyme. Total phenol content was measured using the Folin-Ciocalteu method and brine shrimp test was done to evaluate the toxicity of the extracts. Evaluation of TLC plates alone and after spraying with different reagents indicated that terpenoid was the major component of the sample followed by alkaloid and phenol. Chloroform extract applied more inhibitory effects on GP enzyme activity with percentages of 39.65 in concentration of 2.5 mg/ml. This suppression effect was higher than glucose, as a standard inhibitory agent in the body. The highest amount of phenol was found in the methanol extract, equal to 49 mg GAE g-1. Petroleum ether, chloroform and methanol extracts were considered as non-toxic solvents with LC50 values of 8.9, 3.5 and 3.7 mg/ml respectively. While hexane with 0.089 mg/ml LC50 value was classified as toxic extract. Based on the results of this study, we concluded that Vitis elegans rhizome, has the potential to be further studied for anti-hyperglycemic properties.


1. American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes care. 2012;35:S64-S71.
2. World Health O. Prevention of blindness from diabetes mellitus. World Health Organization. 2006.
3. World Health O. Global report on diabetes. World Health Organization. 2016.
4. Cheng AYY, Fantus IG. Oral antihyperglycemic therapy for type 2 diabetes mellitus. Can Med Assoc J. 2005;172:213-226.
5. American Diabetes A. Standards of medical care in diabetes--2014. Diabetes care. 2014;37:S14.
6. Garber AJ. Long-Acting Glucagon-Like Peptide 1 Receptor Agonists A review of their efficacy and tolerability. Diabetes care. 2011;34:S279-S284.
7. Van De Laar FA, Lucassen PL, Akkermans RP, Van De Lisdonk EH, Rutten GE and Van Weel C. α-Glucosidase Inhibitors for Patients With Type 2 Diabetes Results from a Cochrane systematic review and meta-analysis. Diabetes care. 2005;28:154-163.
8. Patel DK, Kumar R, Laloo D and Hemalatha S. Diabetes mellitus: an overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity. Asian Pac J  Trop Biomed. 2012;2:411-420.
10. Treadway JL, Mendys P and Hoover DJ. Glycogen phosphorylase inhibitors for treatment of type 2 diabetes mellitus. Expert Opin Investg Drugs. 2001;10:439-454.
11. Donnier-Maréchal M, Vidal S. Glycogen phosphorylase inhibitors: a patent review (2013-2015). Expert Opin Ther Pat. 2016;26:199-212.
12. A Sullivan M, E Harcourt B, Xu P, M Forbes J and G Gilbert R. Impairment of liver glycogen storage in the db/db animal model of type 2 diabetes: a potential target for future therapeutics? Curr Drug Targets. 2015;16:1088-1093.
13. Ercan-Fang N, Taylor MR, Treadway JL, Levy CB, Genereux PE, Gibbs EM, Rath VL, Kwon Y, Gannon MC, Nuttall FQ. Endogenous effectors of human liver glycogen phosphorylase modulate effects of indole-site inhibitors. Am J Physiol Endocrinol Metab. 2005;289:E366-E372.
14. Martin WH, Hoover DJ, Armento SJ, Stock IA, McPherson RK, Danley DE, Ralph Stevenson RW, Barrett EJ, Treadway JL. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proc Natl Acad Sci. 1998;95:1776-1781.
15. Goyard D, Kónya B, Chajistamatiou AS, Chrysina ED, Leroy J, Balzarin S, Tournier M, Tousch D, Petit P, Duret C, Maurel P, Somsák L, Docsa T, Gergely P, Praly JP, Azay-Milhau J, Vidal S. Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition. Eur J Med Chem. 2016;108:444-454.
16. Agius L. Role of glycogen phosphorylase in liver glycogen metabolism. Mol Aspects Med. 2015;46:34-45.
17. Oikonomakos NG, Kosmopoulou MN, Leonidas DD, Chrysina ED, Tiraidis C, Bischler N, Tsitsanou E, Zographos SE, Kostas ID, Eisenbrand G. Indirubin and indigo analogues as potential inhibitors of glycogenolysis: structural basis of glycogen phosphorylase inhibition. Indirubin, the red shade of indigo Life in progress editions, Roscoff, France. 2006:177-189.
18. Hayes JM, Kantsadi AL, Leonidas DD. Natural products and their derivatives as inhibitors of glycogen phosphorylase: potential treatment for type 2 diabetes. Phytochem Rev. 2014;13:471-498.
19. Gupta RC, Chang D, Nammi S, Bensoussan A, Bilinski K and Roufogalis BD. Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications. Diabetol Metab Syndr. 2017;9:59.
20. Chang CLT, Lin Y, Bartolome AP, Chen Y-C, Chiu S-C, Yang W-C. Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med. 2013;2013:378657
21. Ayafor JF, Tchuendem MHK, Nyasse B, Tillequin F, Anke H. Novel bioactive diterpenoids from Aframomum aulacocarpos. J Nat Prod. 1994;57:917-923.
22. Ivanovska N, Philipov S. Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions and pure alkaloids. Int J Immunopharmacol. 1996;18:553-561.
23. Nakahara K, Kawabata S, Ono H, Ogura K, Tanaka T, Ooshima T,  Hamada S. Inhibitory effect of oolong tea polyphenols on glycosyltransferases of mutans Streptococci. Appl Environ Microbiol. 1993;59:968-973.
24. Scalbert A. Antimicrobial properties of tannins. Phytochem. 1991;30:3875-3883.
25. Harborne AJ. Phytochemical Methods a Guide to Modern Techniques of Plant Analysis. Springer Science & Business Media. 1998.
26. Wagner H, Bladt S. Plant Drug Analysis:  Thin Layer Chromatography Atlas. Springer Science & Business Media. 1996.
27. Waldi D. Spray reagents for thin-layer chromatography. Thin-layer chromatography, Springer. 1965;483-502.
28. Burden DW, Whitney DB. Protein Isolation and Preparation of Crude Extract. BiotechnologyProteins to PCR, Springer. 1995;59-75.
29. Dubois M, Gilles KA, Hamilton JK, Rebers P, Smith F. Colorimetric method for determination of sugars and related substances. Anal Chem. 1956;28:350-356.
30. Ainsworth EA, Gillespie KM. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteu reagent. Nat Protoc. 2007;2:875-877.
31. Meyer BN, Ferrigni NR, Putnam JE, Jacobsen LB, Nichols DEj, McLaughlin JL. Brine shrimp: a convenient general bioassay for active plant constituents. Planta Med. 1982;45:31-34.
32. Şendoğdu N, Aslan M, Orhan DD, Ergun F, YeŞİLada E. Antidiabetic and antioxidant effects of Vitis vinifera L. leaves in streptozotocin-diabetic rats. Turkish J Pharm Sci. 2006;3:7-18.
33. Nassiri‐Asl M, Hosseinzadeh H. Review of the Pharmacological Effects of Vitis vinifera (Grape) and its Bioactive Constituents: An Update. Phytother Res. 2016;30:1392-1403
34. Alol LH. The Prophylactic Role of Flavonoids of Black Grape (Vitis vinifera L.) on Some Biochemical Parameters in Adult females Rats Treated with Sodium Fluoride. Kufa Journal For Veterinary Medical Sciences. 2015;6
35. Chen J, Mangelinckx S, Adams A, Wang ZT, Li WL, De Kimpe N. Natural flavonoids as potential herbal medication for the treatment of diabetes mellitus and its complications. Nat Prod Commun. 2015;10:187-200.
36. Nazaruk J, Borzym-Kluczyk M. The role of triterpenes in the management of diabetes mellitus and its complications. Phytochem Rev. 2015;14:675-690.
37. Ríos JL, Francini F, Schinella GR. Natural products for the treatment of type 2 diabetes mellitus. Planta Med. 2015;81:975-994.
38. Soman G, Philip G. The nature of the binding site for aromatic compounds in glycogen phosphorylase b. Biochem J. 1975;147:369-371.
39. Kantsadi AL, Apostolou A, Theofanous S, Stravodimos GA, Kyriakis E, Gorgogietas VA, Chatzileontiadou DS, Pegiou K, Skamnaki VT, Stagos D, Kouretas D, Psarra AM, Haroutounian SA, Leonidas DD. Biochemical and biological assessment of the inhibitory potency of extracts from vinification byproducts of Vitis vinifera extracts against glycogen phosphorylase. Food Chem Toxicol. 2014;67:35-43.
40. Nagy L, Docsa T, Szanto M, Brunyanszki A, Hegedűs C, Marton J, Kónya B, Virág L, Somsák L, Gergely P, Bai P. Glycogen Phosphorylase Inhibitor N-(3, 5-Dimethyl-Benzoyl)-N’-(β-D-Glucopyranosyl) Urea Improves Glucose Tolerance under Normoglycemic and Diabetic Conditions and Rearranges Hepatic Metabolism. PloS one. 2013;8:e69420.
41. Ogawa AK, Willoughby CA, Bergeron R, Ellsworth KP, Geissler WM, Myers RW, et al. Glucose-lowering in a db/db mouse model by dihydropyridine diacid glycogen phosphorylase inhibitors. Bioorg Med Chem Lett. 2003;13:3405-3408.42. Docsa T, Marics B, Nemeth J, Huse C, Somsák L, Gergely P, et al. Insulin sensitivity is modified by a glycogen phosphorylase inhibitor: glucopyranosylidene-spiro-thiohydantoin in streptozotocin-induced diabetic rats. Curr Top Med Chem. 2015;15:2390-2394.
43. Baker DJ, Timmons JA, Greenhaff PL. A Systematic Evaluation of Metabolic and Functional Effects in Rat Skeletal Muscle. 2006;10.
44. Karakaya SNEAATS. Antioxidant activity of some foods containing phenolic compounds. Int Jof Food Sci Nutr. 2001;52:501-508.
45. Büyükbalci A, El SN. Determination of in vitro antidiabetic effects, antioxidant activities and phenol contents of some herbal teas. Plant Foods Hum Nutr. 2008;63:27-33.
46.  Patel DK, Kumar R, Prasad SK, Sairam K, Hemalatha S. Antidiabetic and in vitro antioxidant potential of Hybanthus enneaspermus (Linn) F. Muell in streptozotocin–induced diabetic rats. Asian Pac J Trop Biomed. 2011;1:316-322.
47. Ali K, Maltese F, Choi YH, Verpoorte R. Metabolic constituents of grapevine and grape-derived products. Phytochem Rev. 2010;9:357-378.