• Anand S VELTECH
  • Saravanababu C
  • Lakshmi Bs
  • Muthusamy Vs



Objective: Aloe-emodin glycosides (AEG) isolated from Cassia fistula stimulates glucose transport and glycogen storage through a phosphatidylinositol
3 kinase (PI3K)-dependent mechanism in L6 myotubes and inhibits adipocytes differentiation in 3T3L1 adipocytes was previously reported. This
study intended to investigate the insulin mimetic effect of AEG by in vivo method.
Methods: Male Wistar albino rats were randomly allocated into two groups and fed for a period of 3-week. The high-fat diet group animals were
injected with a low dose (35 mg/kg) of streptozotocin to induce Type-2 diabetes. The diabetic rats were then treated with low dose: 10 mg/kg and
high dose: 30 mg/kg for a period of 21-day. A dose-dependent decrease in fasting blood glucose, cholesterol, and triglycerides levels on treatment
with AEG. The carbohydrate metabolism in diabetic rats appeared to improve due to regulation in hepatic enzymes such as hexokinase, glucose-6phosphatase,
and fructose
1,6-bisphosphatase with a concomitant increase
in glycogen
Results: AEG decreased lipid peroxidation and improved the antioxidant (enzymatic and nonenzymatic) levels in the liver of diabetic rats. Treatment
with AEG (30 mg/kg) augmented the phosphorylation of insulin downstream regulators such as insulin receptor beta, insulin receptor substrate 1,
PI3K, glucose transporter 4, glycogen synthase kinase 3 beta, and peroxisome proliferator activator receptor gamma in the skeletal muscle tissue of
the Type-2 diabetic rats compared to vehicle-treated diabetic rats.
Conclusion: The present results suggested that AEG could serve as an interesting candidate in the drug development for the management of diabetes.
Keywords: Aloe-emodin glycoside, Type-2 diabetes, High-fat diet/streptozotocin, Carbohydrate Metabolism, Glycogen, Antioxidant enzyme.


Download data is not yet available.



Ford ES, Li C, Sattar N. Metabolic syndrome and incident diabetes:

Current state of the evidence. Diabetes Care 2008;31(9):1898-904.

de Sousa E, Zanatta L, Seifriz I, Creczynski-Pasa TB, Pizzolatti MG,

Szpoganicz B, et al. Hypoglycemic effect and antioxidant potential

of kaempferol-3,7-O-(alpha)-dirhamnoside from Bauhinia forficata

leaves. J Nat Prod 2004;67(5):829-32.

Valiathan MS. Healing plants. Curr Sci 1998;75:1122-7.

Franconi F, Seghieri G, Canu S, Straface E, Campesi I, Malorni W. Are

the available experimental models of Type 2 diabetes appropriate for a

gender perspective? Pharmacol Res 2008;57(1):6-18.

Zhao S, Chu Y, Zhang C, Lin Y, Xu K, Yang P, et al. Diet-induced

central obesity and insulin resistance in rabbits. J Anim Physiol Anim

Nutr (Berl) 2008;92(1):105-11.

Szkudelski T. The mechanism of alloxan and streptozotocin action in B

cells of the rat pancreas. Physiol Res 2001;50(6):537-46.

Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination

of high-fat diet-fed and low-dose streptozotocin-treated rat: A model

for Type 2 diabetes and pharmacological screening. Pharmacol Res


Sahin K, Onderci M, Tuzcu M, Ustundag B, Cikim G, Ozercan IH,

et al. Effect of chromium on carbohydrate and lipid metabolism in a rat

model of Type 2 diabetes mellitus: The fat-fed, streptozotocin-treated

rat. Metabolism 2007;56(9):1233-40.

Anand S, Muthusamy VS, Sujatha S, Sangeetha KN, Raja RB,

Sudhagar S, et al. Aloe-emodin glycosides stimulates glucose transport

and glycogen storage through PI3K dependent mechanism in L6

myotubes and inhibits adipocytes differentiation in 3T3 L1 adipocytes.

FEBS Lett 2010;584:3170-8.

Brandstrup N, Kirk JE, Bruni C. Determination of hexokinase in

tissues. J Gerentol 1957;12(2):166-71.

Baginsky ES, Foa PP, Zad B. Glucose 6-phosphatase. In: Bergmeyer’s

Methods in Enzymatic Analysis. Vol. 2. New York, NY: Academic

Press; 1974. p. 788-92.

Gancedo JM, Gancedo C. Fructose-1,6-diphosphatase,

phosphofructokinase and glucose-6-phosphate dehydrogenase

from fermenting and non fermenting yeasts. Arch Mikrobiol


Maiti R, Jana D, Das UK, Ghosh D. Antidiabetic effect of aqueous

extract of seed of Tamarindus indica in streptozotocin-induced diabetic

rats. J Ethnopharmacol 2004;92(1):85-91.

Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay

of superoxide dismutase. Indian J Biochem Biophys 1984;21(2):130-2.

Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG,

Hoekstra WG. Selenium: Biochemical role as a component of

Asian J Pharm Clin Res, Vol 9, Suppl. 2, 2016, 191-198

Anand et al.

glutathione peroxidase. Science 1973;179(4073):588-90.

Moron MJ, Diperrie JW, Manner, KB. Levels of glutathione, glutathione

reductase and glutathione-S-transferase by limited proteolysis. J Biol

Chem 1979;260:577-89.

Sangeetha MS, Priyanga S, Hemmalakshmi S, Devaki K. In vivo

antidiabetic potential of Cyclea peltata in streptozotocin induced

diabetic rats. Asian J Pharm Clin Res 2015;8(1):103-8.

Nagasaki M, Nakai N, Oshida Y, Li Z, Xu M, Obayashi M, et al.

Exercise training prevents maturation-induced decreases in insulin

receptor substrate-1 and phosphatidylinositol 3-kinase in rat skeletal

muscle. Metabolism 2000;49(7):954-9.

Srivastava AK, Mishra A, Gautam S, Pal S, Mishra A, Rawat AK,

et al. Effect of Momordica charantia fruits on streptozotocin induced

diabetes mellitus and its associated complications. Int J Pharm Pharm

Sci 2015;7(3):356-63.

Qureshi SA, Ding V, Li Z, Szalkowski D, Biazzo-Ashnault DE, Xie D,

et al. Activation of insulin signal transduction pathway and antidiabetic



small molecule








Liu K, Xu L, Szalkowski D, Li Z, Ding V, Kwei G, et al. Discovery of a

potent, highly selective, and orally efficacious small-molecule activator

of the insulin receptor. J Med Chem 2000;43(19):3487-94.

Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon

extract (traditional herb) potentiates in vivo insulin regulated glucose

utilization via enhancing insulin signaling in rats. Diabetes Res Clin

Pract 2003;62(3):139-48.

Saleem R, Faizi S, Siddiqui BS, Ahmed M, Hussain SA, Qazi A, et al.

Hypotensive effect of chemical constituents from Aloe barbadensis.

Planta Med 2001;67(8):757-60.

Eisenbarth GS, Ziegler AG, Colman PA. Pathogenesis of insulin

dependent (Type 1) diabetes mellitus. Philadelphia, PA: Lea Febiger;

p. 216-39.

Sharma SR, Dwivedi SK, Swarup D. Hypoglycaemic,

antihyperglycaemic and hypolipidemic activities of Caesalpinia

bonducella seeds in rats. J Ethnopharmacol 1997;58(1):39-44.

Radhika R, Krishnakumari S, Sudarsanam D. Antidiabetic activity of

Rheum emodi in alloxan induced diabetic rats. Int J Pharm Sci Res


Gupta BL, Nehal M, Baquer NZ. Effect of experimental diabetes on

the activities of hexokinase, glucose-6-phosphate dehydrogenase and

catecholamines in rat erythrocytes of different ages. Indian J Exp Biol


Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper’s

Biochemistry. 25

ed. Stanford, Connecticut: Appleton & Lange; 2000.

p. 610-7.


Grover JK, Vats V, Rathi SS. Anti-hyperglycemic effect of Eugenia

jambolana and Tinospora cordifolia in experimental diabetes and their

effects on key metabolic enzymes involved in carbohydrate metabolism.

J Ethnopharmacol 2000;73(3):461-70.

Berg JM, Tymoczko JL, Stryer L, editors. Glycolysis and

gluconeogenesis. In: Biochemistry. New York: WH. Freeman and

Company; 2001. p. 425-64.

Saxena A, Bhatnagar M, Garg NK. Enzyme charges in rat tissue during

hyperglycemia. Arogya J Health Sci 1984;10:33-7.

Vats V, Yadav SP, Grover JK. Ethanolic extract of Ocimum sanctum

leaves partially attenuates streptozotocin-induced alterations in glycogen

content and carbohydrate metabolism in rats. J Ethnopharmacol


Bollen M, Keppens S, Stalmans W. Specific features of glycogen

metabolism in the liver. Biochem J 1998;336:19-31.

Gannon MC, Nuttall FQ. Effect of feeding, fasting, and diabetes on liver

glycogen synthase activity, protein, and mRNA in rats. Diabetologia


Hikino H, Kobayashi M, Suzuki Y, Konno C. Mechanisms of

hypoglycemic activity of aconitan A, a glycan from Aconitum

carmichaeli roots. J Ethnopharmacol 1989;25(3):295-304.

Ferrer JC, Favre C, Gomis RR, Fernández-Novell JM, GarcíaRocha


de la Iglesia N, et


Control of glycogen deposition. FEBS



Gayathri M, Kannabiran K. Antidiabetic and ameliorative potential of

Ficus bengalensis bark extract in streptozotocin induced diabetic rats.

Indian J Clin Biochem 2008;23(4):394-400.

Aldini G, Dalle-Donne I, Facino RM, Milzani A, Carini M. Intervention

strategies to inhibit protein carbonylation by lipoxidation-derived

reactive carbonyls. Med Res Rev 2007;27(6):817-68.

Burk RF. Glutathione dependent protection by rat liver microsomal

protein against lipid peroxidation. Biochim Biophys Acta


Helen A, Vijayammal PL. Vitamin C supplementation on hepatic

oxidative stress induced by cigarette smoke. J Appl Toxicol


Wohaieb SA, Godin DV. Alterations in free radical tissue-defense

mechanisms in streptozocin-induced diabetes in rat. Effects of insulin

treatment. Diabetes 1987;36(9):1014-8.

Bhattacharya A, Chatterjee A, Ghosal S, Bhattacharya SK. Antioxidant

activity of active tannoid principles of Emblica officinalis (amla).

Indian J Exp Biol 1999;37(7):676-80.

Ahmed S, Rabman A, Alam A, Saleem M, Athar M, Sultana S.

Evaluation of the efficacy of Lawsonia alba in the alleviation of the

CCl4 induced oxidative stress. J Ethnopharmacol 2000;69(2):57-164.

Anuradha CV, Ravikumar P. Restoration on tissue antioxidants by

fenugreek seeds (Trigonella foenum Graecum) in alloxandiabetic rats.

Ind J Physiol Pharmacol 2001;45(4):408-20.

Goldstein BJ. Protein-tyrosine phosphatases: Emerging targets for

therapeutic intervention in Type 2 diabetes and related states of insulin

resistance. J Clin Endocrinol Metab 2002;87(6):2474-80.



How to Cite

S, A., S. C, L. Bs, and M. Vs. “ALOE-EMODIN GLYCOSIDES AMELIORATE GLUCOSE UTILIZATION VIA INSULIN DOWNSTREAM REGULATORS: AN IN VIVO INVESTIGATION”. Asian Journal of Pharmaceutical and Clinical Research, vol. 9, no. 8, Oct. 2016, pp. 191-8, doi:10.22159/ajpcr.2016.v9s2.13533.



Original Article(s)