This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMSQTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg·bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark., {"references":["Arya, A., Yeng Looi, C., Chuen Cheah, S., Rais Mustafa,M., Ali Mohd,\nM., 2012. Anti-diabetic effects of Centratherum anthelminticum seeds\nmethanolic fraction on pancreatic cells, β-TC6 and its alleviating role in\ntype 2 diabetic rats. J. Ethnopharmacol. 144, 22-32.","Chung, H.S., Shin, J.C., 2007. Characterization of antioxidant alkaloids\nand phenolic acids from anthocyanin-pigmented rice (Oryza sativa cv.\nHeugjinjubyeo). Food Chem. 104, 1670-1677.","Hu, X., Sato, J., Oshida, Y., Xu, M., Bajotto, G., Sato, Y., 2003. Effect\nof Gosha-jinki-gan (Chinese herbal medicine: Niu-Che-Sen-Qi-Wan) on\ninsulin resistance in streptozotocin-induced diabetic rats. Diabetes Res.\nClin. Pract. 59, 103-111.","Jung, U.J., Lee, M.-K., Park, Y.B., Jeon, S.-M., Choi, M.-S., 2006.\nAntihyperglycemic and antioxidant properties of caffeic acid in db/db\nmice. Journal of pharmacology and experimental therapeutics 318, 476-\n483.","King, H., Aubert, R.E., Herman, W.H., 1998. Global burden of diabetes,\n1995–2025: prevalence, numerical estimates, and projections. Diabetes\nCare 21, 1414-1431.","Latiff, A., Faridah Hanum, I., Zainudin Ibrahim, A., Goh, M., Loo, A.,\nTan, H.W., 1999. On the vegetation and flora of Pulau Tioman,\nPeninsular Malaysia. Raffles Bulletin of Zoology 47, 11-72.","Li, A.R., 2007. Phytochemical study on Meiogyne Virgata Blume\nMiq.(annonaceae)/Abd. Rashid Li. Universiti Teknologi MARA\n(UiTM).","Lombardo, Y.B., Chicco, A.G., 2006. Effects of dietary polyunsaturated\nn-3 fatty acids on dyslipidemia and insulin resistance in rodents and\nhumans. A review. The Journal of nutritional biochemistry 17, 1-13.","Mahesh, T., Menon, V.P., 2004. Quercetin allievates oxidative stress in\nstreptozotocin‐induced diabetic rats. Phytother. Res. 18, 123-127.\n[10] Ong, H.C., Ahmad, N., Milow, P., 2011. Traditional medicinal plants\nused by the temuan villagers in Kampung Tering, Negeri Sembilan,\nMalaysia. Ethno Med 5, 169-173.\n[11] Rajavel, V., Sattar, M.Z., Chung, I., Abdulla, M.A., Kassim, N.M.,\nAbdullah, N.A., 2013. Antioxidant and pro-oxidant effects of oil palm\n(Elaeis guineensis) leaves extract in experimental diabetic nephropathy:\na duration-dependent outcome. BMC Complement. Altern. Med. 13,\n242.\n[12] Robertson, R.P., Zhang, H.-J., Pyzdrowski, K.L., Walseth, T.F., 1992.\nPreservation of insulin mRNA levels and insulin secretion in HIT cells\nby avoidance of chronic exposure to high glucose concentrations. J.\nClin. Invest. 90, 320.\n[13] Schuit, F.C., Huypens, P., Heimberg, H., Pipeleers, D.G., 2001. Glucose\nSensing in Pancreatic β-Cells A Model for the Study of Other Glucose-\nRegulated Cells in Gut, Pancreas, and Hypothalamus. Diabetes 50, 1-11.\n[14] Taha, H., Arya, A., Paydar, M., Looi, C.Y., Wong, W.F., Vasudeva\nMurthy, C., Noordin, M., Ali, H.M., Mustafa, A., Hadi, A.H.A., 2014.\nUpregulation of insulin secretion and downregulation of proinflammatory\ncytokines, oxidative stress and hyperglycemia in STZnicotinamide-\ninduced type 2 diabetic rats by Pseuduvaria monticola\nbark extract. Food and Chemical Toxicology 66, 295-306.\n[15] Taha, H., Hadi, A.H.A., Nordin, N., Najmuldeen, I.A., Mohamad, K.,\nShirota, O., Nugroho, A.E., Piow, W.C., Kaneda, T., Morita, H., 2011.\nPseuduvarines A and B, two new cytotoxic dioxoaporphine alkaloids\nfrom Pseuduvaria rugosa. Chemical and Pharmaceutical Bulletin 59,\n896-897."]}