Hypoglycemic activity of the ethyl acetate extract from Smilax glabra Roxb in mice: Biochemical and histopathological studies

Document Type : Original Article


1 Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, Vietnam

2 Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam

3 Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

4 University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam

5 1Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Hanoi, Vietnam

6 School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia


Objective(s): This research was carried out to investigate the hypoglycemic activity of the ethyl acetate (EtOAc) extract from the roots of Smilax glabra Roxb, which strongly exhibit inhibitory activity against α-glucosidase and α-amylase on in vivo type 2 diabetic model.
Materials and Methods: Column chromatography combined with crystallization was used to isolate the active fraction and compounds. Chemical structures of the compounds were determined based on the analysis of the spectroscopic data and comparison with the literature data. The α-glucosidase inhibitory activity (AGI) and the α-amylase inhibitory activity (AAI) were determined quantitatively spectrophotometrically using p-nitrophenyl α-D-glucopyranoside and soluble starch as substrates, respectively. The hypoglycemic activity was examined by evaluating its effects on glucose and insulin levels, insulin resistance, and histopathology of the pancreatic islets and livers in diabetic induced mice administrated with nicotinamide-streptozotocin.
Results: The EtOAc extract and the bioactive compounds astilbin and 5-O-caffeoylshikimic acid in the extract were isolated and confirmed in structures, AGI, and AAI. The treatment at the doses of 500 and 1000 µg/kg of body weight reduced blood glucose levels down to the physiological level of the physical controls in the diabetic mice after two weeks (p <0.05). Moreover, the treatment improved insulin sensitivity. Histopathology analysis showed recovering effects in the size of the pancreatic islets and no damaging effects on the liver after treatment compared with the control group.
Conclusion: Our data suggest that the EtOAc extract possesses hypoglycemic activity and has an antidiabetic potential for therapeutic applications.


1.    Ahamad J, Naquvi K, Mir RS, Ali M, Shuaib M. Review on role of natural alpha-glucosidase inhibitors for management of diabetes mellitus. IJBR 2011; 2:374-380.
2.    Kalra S. Alpha-glucosidase inhibitors. J Pak Med Assoc 2014; 64:474-476.
3.    Kang W. Alpha glucosidase inhibitory in vitro and antidiabetic activity in vivo of Osmanthus fragrans. J Med Plants Res 2012; 6:2850-2856.
4.    Nishibori N, Sawaguchi M, Hiroi T. Inhibitory effects of aqueous extract prepared from joint part of lotus root on alpha-amylase and alpha-glucosidase activities. Phytopharmacology 2012; 3:1-11.
5.    Tafesse TB, Hymete A, Mekonnen Y, Tadesse M. Antidiabetic activity and phytochemical screening of extracts of the leaves of Ajuga remota Benth on alloxan-induced diabetic mice. BMC Compl Altern Med 2017; 17:243.
6.    Tasnuva ST, Qamar UA, Ghafoor K, Sahena F, Jahurul MHA, RukshanaAH, Juliana MJ, Al-Juhaimi FY, Jalifah L, Jalal KCA, Ali ME, Zaidul ISM. Alpha-glucosidase inhibitors isolated from Mimosa pudica L. J Nat Prod 2017; 27:1-5.
7.    Johnson OO, Zhao M, Gunn J, Santarsiero BD, Yin ZQ, Ayoola GA, Coker HA, Che CT. Alpha-glucosidase inhibitory prenylated anthranols from Harungana madagascariensis. J Nat Prod 2016; 79:224-229.
8.    Zhang L, Chen Q, Li L, Kwong JSW, Jia P, Zhao P, Wang W, Zhou X, Zhang M, Sun X. Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis. Sci Rep 2016; 6:326-349.
9.    Tiwari P, Ahmad K, Baig MH. Gymnema sylvestre for diabetes: From traditional herb to future’s therapeutic. Curr Pharm 2017; 23:1667-1676.
10.    Do TL. The medical plants and natural drugs in Viet Nam. Medicine Publishing House, Hanoi, Vietnam. 2000.
11.    Nguyen PTM, Ngo VQ, Nguyen THM, Maccarone AT, Pyne SG. α-Glucosidase inhibitory activity of the extracts and major phytochemical components of Smilax glabra Roxb. Nat Prod J 2020; 10:26-32.
12.    Xu S, Shang MY, Liu GX, Xu F, Wang X, Shou CC, and Cai SQ. Chemical constituents from the rhizomes of Smilax glabra and their antimicrobial activity. Molecules 2013; 18: 5265-5287.
13.     Xiao Z, Storms R, Tsang A. A quantitative starch-iodine method for measuring alpha-amylase and glucoamylase activities. Anal Biochem 2006; 351:146-148.
14.    Birgani GA, Ahangarpour A, Khorsandi L, Moghaddam HF. Anti-diabetic effect of betulinic acid on streptozotocin- nicotinamide induced diabetic male mouse model. Bra J Phar Sci 2018;54(2):e17171.
15.    Dube S, Errazuriz I, Cobelli C, Basu R, Basu A. Assessment of insulin action on carbohydrate metabolism: physiological and non-physiological methods. Diabetic Med 2013; 30:664-670.
16.    Li B, Lin W, Lin N, Dong X and Liu L. Study of the correlation between serum ferritin levels and the aggregation of metabolic disorders in non-diabetic elderly patients. Exp Ther Med 2014; 7:1671-1676.
17.    Ma Y, Wang Y, Huang Q, Ren Q, Chen S, Zhang A, et al. Impaired β cell function in Chinese newly diagnosed type 2 diabetes mellitus with hyperlipidemia. J Diabetes Res 2014; 2014:ID493039.
18.    Dao VP, Nguyen NX, Do NT. Hypoglycemic activity of Smilax Glabra Roxb on experimental animals. J Med Exp 2004; 32:17-25.
19.    Nguyen NX, Dao VP, Nguyen TBT. Hypoglycemic activity by oral administration of Smilax glabra roxb, liliaceae – Sg on mice and its effects on glucose tolerance. J Med Exp 2014; 42:20-24.
20.    Chia YY, Liong SY, Ton SH, Kadir KB. Amelioration of glucose homeostasis by glycyrrhizic acid through gluconeogenesis ratelimiting enzymes. Eur J Pharmacol 2012; 677:197-202.
21.    Karthic K, Kirthiram KS, Sadasivam S, Thayumanavan B. Identification of α-amylase inhibitors from Syzygium cumini Linn Seeds. Indian J Exp Biol 2008; 46:677-680.
22.    Lee J, Yee ST, Kim JJ, Choi MS, Kwon EY, Seo KI, Lee MK. Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice. Chem Biol Interact 2010; 188:635-642.
23.    Jiang DJ, Li ZN. Nicotinamide overload may play a role in the development of type 2 diabetes. World J Gastroenterol 2009; 15:5674-5684.
24.    Szkudelski T. Streptozotocin–nicotinamide-induced diabetes in the rat characteristics of the experimental model. Exp Biol Med 2012; 237:481-490.
25.    Adolfo Andrade-Cetto A, and Medina-Hernández AE. Hypoglycemic effect of Bromelia plumieri (E. Morren) L.B. Sm., leaves in STZ-NA-induced diabetic rats. Front Pharmacol 2013; 4:1-4.
26.    Adiga S, Bairy KL, Meharban A, Punita LSR. Hypoglycemic effect of aqueous extract of  Trichosanthes dioica in normal and diabetic rats. Int J Diabetes Dev Ctries 2010; 30:38–42.
27.    Fukunaga T, Miura T, Furuta K, Kato A. Hypoglycemic effect of the rhizomes of Smilax glabra in normal and diabetic mice. Biol Pharm Bull 1997; 20:44–46.
28.    Wang X, Chen Y, Abdelkader D, Hassan W, Sun H, Liu J. Combination therapy with oleanolic acid and metformin as a synergistic treatment for diabetes. J Diabetes Res 2015; ID973287.
29.    Trinh TTV, Vu VC, Pham TH, Pham VC, Nguyen QV. Antioxidant activity of extracts and astilbin from the root of Smilax glabra of Vietnam. Malaysian J Chem 2015; 17:12-19.
30.    Sen S, Roy M, Chakraborti AS. Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats. J Pharm Pharmacol 2011; 63:287-296.
31.    Jang SM, Yee ST, Choi J, Choi MS, Do GM, Jeon SM. Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. Int Immunopharmacol 2009; 9:113-119.
32.    Kasai, R.; Hirono, S.; Chou, W.; Tanaka, O.; Chen F. Sweet dihydroflavonol rhamnoside from leaves of Engelhardtia chrysolepis, a Chinese folk medicine, Hung-qi. Pharm Bull 1988, 36:4167–4170.
33.    Fukuoka, M. Chemical and toxicological studies on Bracken Fern, Pteridium aquilinum Var. latiusculum VI. Isolation of 5-O-caffeoylshikimic acid as an antithiamine factor. Chem Pharm Bull 1982, 30:3219–3224.