BackgroundCoscinium fenestratum (CF) (Gaertn.) Colebr is from the family Menispermaceae, is a woody plant found in Southeast Asia including Malaysia. Traditionally CF has been used for the treatment of many diseases including diabetes Mellitus. Our previous research identified Palmatine a protoberberine alkaloid to be the active bioactive compound present in CF.ObjectiveThe aim of this study was to investigate in vitro and in vivo anti‐diabetic, antioxidant Effect on High Fat Diet Induced Diabetic Rat Module.MethodThe ability of Palmatine to inhibit reactive oxygen specie (ROS) such as Lipid peroxidation, DPPH, Nitric oxide, Hydroxyl, free radical scavenging activity was evaluated. The in vitro antidiabetic activity of Palmatine was evaluated using alpha glycosidase, alpha amylase and Dipeptidyl peptidase IV enzyme. Sprague dawley rats weighing 180–200g was fed with high fat diet (HFD) for 60 days to induce diabetes. Rats with plasma glucose level of 11mmol/L or 200mg/dL and above after 60 days HFD feeding, were orally administered with Palmatine (2mg/kg) for 90 days. The plasma glucose level and body weight of the rats were measured weekly. After treatment, the rat blood was withdrawn via cardiac puncture for hematological studies. Liver and pancreas was harvested for antioxidant, histology, biochemical and lipid profile analysis.ResultPalmatine was able to inhibit free radicals generated by Nitric oxide, DPPH, Hydroxyl, and alpha glucosidase, and alpha amylase activities. Palmatine was able to reduce plasma glucose level, activate antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and inhibit lipid peroxidation in HFD induced diabetic rats. Biochemical and hematological analysis showed a reduction of diabetic markers in rats such HbA1c, urea, alkaline phosphatase, aspartate transaminase, alanine aminotransferase, LDL‐cholesterol, Triglycerides, but increase HDL level.ConclusionPalmatine possess antidiabetic and antioxidant in HFD induced diabetic rat model and able to offer protection to kidney, liver and cardiovascular organs by reducing the disease markers (Diabetes Complication Prevention).Support or Funding InformationCentre of Excellence for Research, Value, Innovation and Entrepreneurship Research Grant Scheme UCSI University (UCSI‐CERVIE‐RGS Proj‐in‐FAS 039)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.