Biochemical and Oxidative Changes in High Fat Diet/Streptozotocin-induced Diabetic Rats Treated with Metformin and the Polyherbal Diawell

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O. N. Briggs
E. O. Nwachuku
D. Tamuno-Emine
N. Nsirim
K. N. Elechi-Amadi


Diabetes mellitus is an epidemic, with a huge disease burden on the patients. This has led to an increase in the use of herbal remedies and combination therapies to reduce this burden.

Aim: This study evaluates the biochemical and oxidative changes in type 2 diabetic rats, treated with metformin and the polyherbal drug diawell.

Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Fasting plasma insulin (FPI), total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance (IR) was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) method. Oxidative stress index (OSI) was determined by the ratio of TOS to TAS. Phytochemical analysis was also done on the herbal tablet.

Results: Mean FPG levels were significantly lower (p˂0.05) in all groups, except the group administered diawell, which was not significantly different (p>0.05), compared to the diabetic control. Mean FPG levels were significantly higher (p˂0.05) in the metformin group, diawell group, but showed no significant difference (p>0.05) in the combination group, compared to the negative control. HOMA-IR was significantly higher (p<0.05) in the diabetic control compared to the negative control and treatment groups. The metformin and diawell groups had significantly higher (p˂0.05) HOMA-IR values, whereas the combination (metformin + diawell) showed no significant difference (p>0.05) when compared to the negative control. TOS was significantly higher (p<0.05) in the diabetic control compared to the negative control and treatment groups. The metformin and diawell groups had significantly higher (p˂0.05) TOS values, whereas the combination (metformin + diawell) showed no significant difference (p>0.05) when compared to the negative control. There was significantly lower (p˂0.05) TAS levels in the diabetic and treatment groups, compared to the negative control. OSI values were significantly lower (p˂0.05) in all groups when compared to the diabetic control. Also, OSI values were significantly higher (p˂0.05) in the treatment groups compared to the negative control.

Conclusion: There was depletion of antioxidant parameters and an increase in oxidative stress in the diabetic rats. Administration of metformin and the polyherbal tablet diawell individually, were not effective in correcting the pathological and biochemical changes associated with diabetes. However, the combination treatment produced a better glycaemic response and attenuated the oxidant status in the rats. Antioxidant therapy should be incorporated in diabetes management, and anti-diabetic herbals properly evaluated.

Diabetes mellitus, oxidative stress, antioxidants, herbal therapy, insulin resistance, diawell, metformin, streptozotocin.

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How to Cite
Briggs, O. N., Nwachuku, E. O., Tamuno-Emine, D., Nsirim, N., & Elechi-Amadi, K. N. (2019). Biochemical and Oxidative Changes in High Fat Diet/Streptozotocin-induced Diabetic Rats Treated with Metformin and the Polyherbal Diawell. Journal of Complementary and Alternative Medical Research, 7(4), 1-11.
Original Research Article


American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(1): 62-69.

Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice. 2010;87(1):4-14.

Briggs ON, Brown H, Elechi-amadi K, Ezeiruaku F, Nduka N. Superoxide dismutase and glutathione peroxidase levels in patients with long standing type 2 diabetes in Port Harcourt, Rivers State, Nigeria. International Journal of Science and Research. 2016;5(3):1282-1288.

Bashan N, Kovsan J, Kachko I, Ovadia H, Rudich A. Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species. Physiological Reviews. 2009;89:27-71.

Krentz JA, Bailey CJ. Oral antidiabetic agents: Current role in type 2 diabetes mellitus. Drugs. 2005;65(3):385– 411.

Yang WC, Srinivas Nammi S, Jeppesen PB, Cho WCS. Complementary and alternative medicine for diabetes. Evidence-Based Complementary and Alternative Medicine. 2013;831068.

Medagama AB, Bandara R. The use of Complementary and Alternative Medicines (CAMs) in the treatment of diabetes mellitus: Is continued use safe and effective? Nutrition Journal. 2014;13: 102.

Kumar D, Bajaj S, Mehrotra R. Knowledge, attitude and practice of complementary and alternative medicines for diabetes. Public Health. 2006;120(8): 705–711.

Organisation for economic co-operation and development. Guidance document on acute oral toxicity testing: Environmental Health and Safety Monograph Series on Testing and Assessment No. 24. 2001;24.
(Accessed 14th July, 2018)

Paget GE, Barnes JM. Evaluation of drug activities. In Lawrence DR, Bacharach AL. (Eds.). Pharmacometrics. New York: Academy Press. 1964;161.

Breyer MD, Bottinger E, Brosius FC, Coffman TM, Harris RC, Heilig CW, Sharma K. Mouse models of diabetic nephropathy. Journals of the American Society of Nephrology. 2005;16: 27-45.

Furman BL. Streptozotocin-induced diabetic models in mice and rats. Current Protocols in Pharmacology. 2015;70(5):1-20.

Barham D, Trinder P. An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst. 1972;97(151):142-145.

Engvall E, Perlmann P. Enzyme-linked immunosorbent assay, elisa. The Journal of Immunology. 1972;109(1):129-135.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28(7):412-419.

Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical Biochemistry. 2004;37:277-285.

Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry. 2005;38:1103-1111.

Ezeonu CS, Ejikeme CM. Qualitative and quantitative determination of phytochemical contents of indigenous nigerian softwoods. New Journal of Science. 2016;5601327.

Kaur R, Afzal M, Kazmi I, Ahamd I, Ahmed Z, Ali B, Ahmad S, Anwar F. Polypharmacy (Herbal and synthetic drug combination): a novel approach in the treatment of type-2 diabetes and its complications in rats. Journal of Natural Medicines. 2013;67(3): 662-671.

Van-Wyk BE, Wink M. Phytomedicines, herbal drugs and poisons. Briza, Kew Publishing, Cambridge University Press: Cambridge, UK; 2015.

Lu HE, Jian CH, Chen SF, Chen TM, Lee ST, Chang CS, Wenz CF. Hypoglycaemic effects of fermented mycelium of Paecilomyces farinosus (G30801) on high-fat fed rats with streptozotocin-induced diabetes. Indian Journal of Medical Research. 2010;131:696–701.

Skovso S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. Journal of Diabetes Investigation. 2014;5: 349-358.

Poonam T, Prakash GP, Kumar LV. Effect of co-administration of Allium sativum extract and metformin on blood glucose of streptozotocin induced diabetic rats. Journal of Intercultural Ethnopharmacology. 2013;2:81–84.

Oluwayemi AT, Nwachuku EO, Holy B. Effects of the interation of metformin and Vernonia amygdalina (Bitter leaf) on steptozotocin-induced diabetic rats. Asian Journal of Biochemistry, Genetics and Molecular Biology. 2018;1(2):1-8.

Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM. A new rat model of type 2 diabetes: The fat-fed, streptozotocin-treated rat. Metabolism. 2000;49:1390-1394.

Yoon SH, Han EJ, Sung JH, Chung SH. Anti-diabetic effects of compound K versus metformin versus compound K-metformin combination therapy in diabetic db/db mice. Biological and Pharmaceutical Bulletin. 2007;30(11):2196–2200.

Gupta RC, Chang D, Nammi S, Bensoussan A, Bilinski K, Roufogalis BD. Interactions between antidiabetic drugs and herbs: An overview of mechanisms of action and clinical implications. Diabetology & Metabolic Syndrome. 2017; 9(59):1-12.

Zhang Y, Hu T, Zhou H, Zhang Y, Jin G, Yang Y. Antidiabetic effect of polysaccharides from Pleurotus ostreatus in streptozotocin-induced diabetic rats. International Journal of Biological Macromolecules. 2016;83:126-132.

Hu X, Cheng D, Zhang Z. Antidiabetic activity of Helicteres angustifolia root. Pharmaceutical Biology. 2016;54(6):938-944.

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circulation Research. 2010;107(9):1058-1070.

Chen LH, Chien YW, Chang ML, Hou CC., Chan CH, Tang HW, Huang HY. Taiwanese green propolis ethanol extract delays the progression of type 2 diabetes mellitus in rats treated with streptozotocin/high-fat diet. Nutrients. 2018;10:503.

Asadi S, Goodarzi MT, Karimi J, Hashemnia M, Khodadadi I. Does curcumin or metformin attenuate oxidative stress and diabetic nephropathy in rats? Journal of Nephropathology. 2019;8(1):8.

Lanjhiyana S, Garabadu D, Ahirwar D, Rana AC, Ahirwar B, Lanjhiyana SK. Pharmacognostic standardization and hypoglycemic evaluations of novel polyherbal formulations. Der Pharmacia Lettre. 2011;3(1):319-333.

Maninder-Kaur VV. Diabetes and antidiabetic herbal formulations: an alternative to Allopathy. International Journal of Pharmacognosy. 2014;1(10): 614-626.

Balamash KS, Alkreathy HM, Al-Gahdali EH, Khoja SO, Ahmad A. Comparative biochemical and histopathological studies on the efficacy of metformin and virgin olive oil against streptozotocin-induced diabetes in Sprague-Dawley rats. Journal of Diabetes Research. 2018;20:4692197.