Glucose utilization and anti-oxidative mechanisms of the aqueous hunteria umbellata seed extract in alloxan-induced diabetic rats
Keywords:
Hunteria umbellata, Alloxan-induced diabetes, Fasting blood glucose, Liver glycogen, Glucose-6-phosphatase, Oxidative stress markersAbstract
Summary: In South-west Nigeria, water decoctions of Hunteria umbellata seeds are highly valued by traditional healers in the local management of diabetes mellitus, obesity and hyperlipidemia. Previous studies hypothesized one of the antihyperglycemic mechanisms of the aqueous seed extract of Hunteria umbellata (HU) to be mediated probably via increased peripheral glucose utilization. The present study, therefore, was designed at evaluating the peripheral glucose utilization and anti-oxidative mechanisms of 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in alloxan-induced diabetic rats in Groups IV-VI rats as well as in the control groups (Groups I-III). Experimental type 1 DM was induced in male Wistar rats through intraperitoneal injection of 150 mg/kg of alloxan monohydrate in cold 0.9% normal saline after which the diabetic rats were orally treated with 50-200 mg/kg of HU for 14 days. Effects of HU on the rat body weight, percentage body weight changes and fasting blood glucose (FBG) were determined on days 1 and 15 of the experiment. Also, on day 15 of the experiment, HU effect on serum insulin, liver enzyme markers, proteins, albumin, triglyceride, total cholesterol and lactate dehydrogenase as well as on hepatic tissue oxidative stress markers, liver glycogen and glucose-6-phosphatase were determined after sacrificing the rats under diethyl ether anesthesia. Results showed that oral treatments with 50-200 mg/kg of HU caused significant (p<0.0001) improvements in the weight loss caused by alloxan-induced diabetes, while causing significant (p<0.05, p<0.001 and p<0.0001) dose-related reductions in the FBG levels despite causing non-significant (p>0.05) alterations in the serum INS levels in the treated rats. Also, repeated oral treatment with HU caused significant (p<0.0001) reversal in the decrease and increase in the hepatic glycogen levels and glucose-6-phosphatase activity, respectively, caused by alloxan-induced diabetes. Similar significant (p<0.0001) and complete reversal effects were recorded in the serum hepatic enzyme markers, total protein, albumin, triglyceride, total cholesterol and lactate dehydrogenase as well as on hepatic tissue oxidative stress markers such as superoxidase dismutase (SOD), catalase (CAT), malonialdehyde (MDA) and reduced glutathione (GSH) of HU-treated rats when compared to that of untreated alloxan-induced diabetic rats. In conclusion, results of this study showed HU treatment to significantly ameliorate the hyperglycemia and oxidative stress in alloxan-induced diabetic rats which was mediated via increased hepatic glycogen deposit, decreased hepatic glucose-6-phosphatase activity and improvement in antioxidant/free radicals scavenging activities.
References
Abdulrahman, M.M., El-Hefnawy, M.H., Aly, R.H., et al. (2013). Metabolic effects of honey in type 1 diabetes mellitus: a randomized crossover pilot study. Journal of Medicinal Food 16(1): 66-72.
Adeneye, A.A. and Adeyemi, O.O. (2009a). Hypoglycemic effects of the aqueous seed extract of Hunteria umbellata in normal and glucose- and nicotine-inducedhyperglycemic rats. International Journal of Applied Research and Natural Products 2(1): 9-18.
Adeneye, A.A. and Adeyemi, O.O. (2009b). Further evaluation of the antihyperglycemic effect of Hunteria umbellata (K. Schum.) Hallier f. seed extract in experimental diabetes. Journal of Ethnopharmacology 126(2): 238-243.
Adeneye, A.A., Adeyemi, O.O., Agbaje, E.O. (2010). Anti-obesity and antihyperlipidemic effect of Hunteria umbellata seed extract in experimental hyperlipidemia. Journal of Ethnopharmacology 130(2): 307-314.
Adeneye, A.A., Crooks, P.A., Fadhel-Albayati, Z., et al. (2013). Antihyperglycemic profile of erinidine isolated from Hunteria umbellata seed. African Journal of Traditional, Complementary and Alternative Medicine 10(2): 189-202.
Adeneye, A.A., Crooks, P.A., Miller, A-F., et al. (2012). Isolation and structure elucidation of a new indole alkaloid, erinidine, from Hunteria umbellata seeds. Pharmacologia 3(7): 204-214.
Adeneye, A.A., Sofidiya, M.O., Adenekan, O.S. (2011). Anti-inflammatory and antioxidant activities of Hunteria umbellata seed fractions. Pharmacologia 2(6): 165-171.
Baginsky, E.S., Foa, P.P., Zak, B. (1992). In: Bergmeyer, H.U. and Gawehn, K. (eds). Methods of enzymatic analysis, 2nd edition. Academic Press, New York, pp. 876-880.
Bouche, C., Serdy, S., Kahn, C.R., et al. (2004). The cellular fate of glucose and its relevance in type 2 diabetes. Endocrine Reviews 25: 807-830.
Carroll, N.V., Longley, R.W., Roe, J.H. (1956). The determination of glycogen in liver and muscle by use of anthron reagent. Journal of Biological Chemistry 220: 583-593.
Ceriollo, A. (2006). Oxidative stress and diabetes-associated complications. Endocrine Practice 12(Suppl1): 60-62.
Chattopadhyay, R.R., Sakar, S.K., Ganguly, S., et al. (1992). Effect of leaves of Vinca rosea Linn. on glucose utilization and glucose deposition by isolated rat hemi-diaphragm. Indian Journal of Physiology and Pharmacology 36: 137-138.
Clore, J.N., Stillman, J., Sugerman, H. (2000). Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes. Diabetes 49(6): 967-974.
Djordjevic, A., Spasic, S., Jovanovic-Galovic, A., et al. (2004). Oxidative stress in diabetic pregnancy: SOD, CAT and GSH-Px activity and lipid peroxidation products. Journal of Maternal, Fetal and Neonatal Medicine 16: 367-372.
Domínguez, C., Ruiz, E., Gussinye, M., et al. (1998). Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents. Diabetes Care 21(10): 1736-1742.
Doumas, B.T., Watson, W.A., Biggs, H.G. (1971). Albumin standard and the measurement of serum albumin and bromocresol green. Clinica Chimica Acta 31: 131-137.
Ezekwesili, C.N., Ogbunugafor, H.A., Ezekwesili-Ofili, J.O. (2012). Antidiabetic activity of aqueous extract of Vitex dodiana leaves and Cinchona calisaya bark in alloxan-induced diabetic rats. International Journal of Tropical Disease and Health 2(4): 290-300.
Falodun, A., Nworgu, Z.A.M., Ikponmwonsa, M.O. (2006). Phytochemical components of Hunteria umbellata (K. Schum.) and its effect on isolated non-pregnant rat uterus in oestrus. Pakistani Journal of Pharmaceutical Sciences 19(3): 256-258.
Feillet-Coudray, C., Rock, E., Coudray, C. (1999). Lipid peroxidation and antioxidant status in experimental diabetes. Clinica Chimica Acta 284: 31-43.
Frier, B.M. and Fisher, M. (2010). Diabetes mellitus. In: Colledge, N.R., Walker, B.R., Ralston, S.H. (eds.). Davidson’s Principles and Practice of Medicine, 21st edition. Churchill Livingstone Elsevier, Edinburg, pp. 795-834.
Goldberg, D.M., Martin, J.V., Knight, A.H. (1977). Elevation of serum alkaline phosphate activity and related enzymes in diabetes mellitus, Clinical Biochemistry 10(1): 8-11.
Gupta, M.P., Solis, N.G., Avella, M.E., et al. (1984). Hypoglycemic activity of Neurolaena lobata. Journal of Ethnopharmacology 10: 323-327.
Herbert, V., Lau, K.S., Gottlieb, C.W., et al. (1965). Coated charcoal immunoassay of insulin. Journal of Clinical Endocrinology and Metabolism 25: 375-384.
Hunt, J., Dean, R.T., Wolff, S.P. (1988). Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes and ageing. Biochemical Journal 256: 205-212.
Igbe, I., Omogbai, E.K.I., Ozolua, R.I. (2009). Hypoglycemic activity of aqueous seed extract of Hunteria umbellata in normal and streptozotocin-induced diabetic rats. Pharmaceutical Biology 47(10): 1011-1016.
Iwalewa, E.O., Adewale, I.O., Taiwo, B.J., et al. (2008). Effects of Harungana madagascariensis stem bark extract on the antioxidant markers in alloxan-induced diabetic and carrageenan-induced inflammatory disorders in rats. Journal of Complementary and Integrative Medicine 5(1): 1-18.
Kakkar, P., Dos, B., Viswanathan, P.N. (1984). A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry and Biophysics 21: 130-132.
Kaneto, H., Katakami, N., Kawamori, D., et al. (2007). Involvement of oxidative stress in the pathogenesis of diabetes. Antioxidant and Redox Signaling 9: 355-366.
Kaur, G., Jabbar, Z., Anthar, M., et al. (2006). Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food and Chemical Toxicology 44: 984-993.
Kingsley, S.R. and Frankel, S.J. (1939). The determination of serum total protein, albumin and globulin by the biuret reaction. Journal of Biological Chemistry 128: 131-137
Kumar, R.P., Sujatha, D., Saleem, T.S.M., et al. (2010). Potential antidiabetic and antioxidant activities of Morus indica and Asystasia gangetica in alloxan-induced diabetes mellitus. Journal of Experimental Pharmacology 2: 29-36.
Lawrence, J.C. and Roach, P.J. (1997). New insights into the role and mechanism of glycogen synthase activation by insulin. Diabetes 46: 541-547.
Lenzen, S. (2008a). The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 51(2): 216-226.
Lenzen, S. (2008b). Oxidative stress: vulnerable beta-cell. Biochemical Society Transactions 36(Pt 3): 343-347.
Liu, Z., Barrett, E.J., Dalkin, A.C., et al. (1994). Effect of acute diabetes on rat hepatic glucose-6-phosphatase activity and its messenger RNA level. Biochemical and Biophysical Research Communications 205(1): 680-686.
Maiese, K., Chong, Z.Z., Shang, Y.C. (2007). Mechanistic insights into diabetes mellitus and oxidative stress. Current Medicinal Chemistry 16(16): 1729-1738.
McGrowder, D.A., Anderson-Jackson, L., Crawford, T.V. (2013). Biochemical evaluation of oxidative stress in type 1 diabetes. In: Escher, A.P. and Li, A. (eds). Diabetes type 1. InTech Publishing Co., Crotia, pp. 223-248. DOI: 10.5772/52836.
Moss, D.W. and Henderson, A.R. (1999). Clinical enzymology. In: Burtis, C.A. and Ashwood, E.R. (eds). Tietz’s Textbook of Clinical Chemistry, 3rd edition. WB Saunders, Philadelphia, pp. 617-721.
Niedowicz, D. and Daleke, D. (2005). The role of oxidative stress in diabetic complications. Cell Biochemistry and Biophysics 43: 289-330.
Petersen, K.F., Befroy, D., Dufour, S., et al. (2003). Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300(5622): 1140-1142.
Rajaram, K. (2013). Antioxidant and antidiabetic activity of Tectona grandis Linn. in alloxan
induced albino rats. Asian Journal of Pharmaceutical and Clinical Research 6(Suppl 3): 174-177.
Niger. J. Physiol. Sci. 29 (2014): Adeneye et al
Peripheral glucose utilization mechanisms of Hunteria Umbellata seed extract 79
Rahul, S., Sanjay, K., Abhay, K.S. (2006). Antidiabetic potential of Butea monosperma in rats. Fitoterapia 77: 86-90.
Raju, J., Gupta, D., Rao, A.R., et al. (2001). Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes. Molecular and Cellular Biochemistry 224(1-2): 45-51.
Rao, G.M., Morghom, L.O., Kabur, M.N., et al. (1989). Serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels in diabetes mellitus. Indian Journal of Medical Sciences 43(5): 118-121.
Robertson, R.P. (2004). Chronic oxidative stress as central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. Journal of Biological Chemistry 279(41): 42351-42354.
Robertson, R.P., Harmon, J., Tran, P.O., et al. (2003). Glucose toxicity in β-cells: Type 2 diabetes, good radicals gone bad, and glutathione connection. Diabetes 52(3), 581-587.
Shirwaikar, A., Rajendran, K., Kumar, C.D., et al. (2004). Antidiabetic activities of aqueous leaf extract of Annona squamosa in streptozotocin-nicotinamide type 2 diabetic rats. Journal of Ethnopharmacology 91: 171-175.
Sinha, A.K. (1972). Colorimetric assay of catalase. Analytical Biochemistry 47: 389-394.
Stanely, M.P.P. and Menon, V.P. (2001). Antioxidant action of Tinospora cordifolia root extract in
alloxan diabetic rats. Phytotherapy Research 15: 213-218.
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (2002). Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 25(Suppl.l): S5-S20.
Trinder, P. (1969). Determination of blood glucose using 4-aminophenzone as oxygen acceptor. Journal of Clinical Pathology 22: 246-248.
Turk Z. (2010). Glycotoxines, carbonyl stress and relevance to diabetes and its complications.
Physiological Research 59: 147-156.
United States National Institutes for Health. (1985). Publication no. 85-23.
Venogopal, P.M., Prince, P.S.M., Pari, L. (1998). Hypoglycemic activity of Syzigium cumini seeds: effect on lipid peroxidation in alloxan diabetic rats. Journal of Ethnopharmacology 61: 1-7.
Wild, S., Roglic, G., Green, A., et al. (2004). Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27: 1047-1053.
Wroblewski, F. and LaDue, J.S. (1955). Lactic dehydrogenase activity in blood. Proceedings of Society for Experimental Biology and Medicine 90: 210-213.
Zappacosta, B., De Sole, P., Rossi, C., et al. (1995). Lactate dehydrogenase activity of platelets in diabetes mellitus. European Journal of Clinical Chemistry and Clinical Biochemistry 33(8): 487-489.
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