27 Background: Dillenia indica (D. indica) can suppress carbohydrates 28 hydrolysis by inhibiting α-amylase and α-glucosidase. However, there is a lack 29 of understanding of its therapeutic potential as an antidiabetic and anti-30 hyperlipidemic agent. 31Methods and findings: Type 2 diabetes (T2D) was induced by a single 32 intraperitoneal injection of Streptozotocin (STZ; 90mg/kg) and hyperlipidemia 33 by feeding with 1% cholesterol, 5% coconut oil and 5% cow fat diet. 34Administration of D. indica extracts in water for four weeks triggered a 35 significant (p≤0.05) reduction in fasting serum glucose (FSG) levels with 36 concomitant improvement in serum insulin levels. Both the water-and 37 ethanol-extract of D. indica treated groups showed significant (p≤0.01) 38 reduction in total cholesterol levels by 25% and 19%, respectively. HDL-39 cholesterol was also augmented (by 14%) in ethanol-extract treated group. 40Liver glycogen content was higher in the water-extract treated group. 41Histopathological examination revealed that there was no tubular epithelial 42 cell degeneration or necrosis in the renal tissues or hepatocyte degeneration 43 and sinusoidal dilation in liver tissues in animals that received the water-44 extract. On the other hand, consumption of D. indica extract with 1% 45 cholesterol, 5% coconut oil diet or with a 5% cow fat diet for 14 days 46 significantly reduced serum cholesterol levels in group-lll (60→45 mg/dl; 47 p≥0.05) and -IV (85→66 mg/dl; p≥0.05) hypercholesterolemic model rats. D. 48 indica fruit extract also reduced serum TG levels (Group-III: 87→65 mg/dl; 49 Group-IV: 40→90 mg/dl; p≥0.05). Interestingly, treatment with D. indica Page 3 of 52 50 prevented a reduction in serum HDL levels in those hypercholesterolemic 51 model rats. Serum LDL levels were significantly lower in group-III (47→39 52 mg/dl; p≥0.05) and group-IV (57→44 mg/dl; p≥0.05) hypercholesterolemic 53 model rats after D. indica treatment. 54 Conclusion: D. indica fruit ameliorates FSG, insulin secretion, glycogen 55 synthesis, and serum lipid profile. Therefore, D. indica fruit can be a potential 56 therapeutic agent for diabetic and hyperlipidemia. Introduction 75 Diabetes mellitus is a chronic metabolic disorder characterized by on-going 76 hyperglycemia. Insulin resistance and decreased insulin secretion are the two 77 cardinal features of type 2 diabetes mellitus (T2DM). T2DM is typically 78 diagnosed based on glucose levels, either a fasting plasma glucose (FPG) ≥ 79 7.0 or a 2-hour 75 g oral glucose tolerance test (OGTT) ≥ 11.1 mmol/L levels. 80 Pre-diabetic classifications include a fasting blood glucose (FBG) of 5.6-81 6.9 mmol/L or a 2-hour blood glucose level of ≥7.8 and < 11.1 mmol/L [1]. 82 T2DM is often accompanied by cardiovascular disease, diabetic neuropathy, 83 nephropathy, and retinopathy. An altered lipid profile is common in T2DM 84 patients. Furthermore, reduced hepatic glycogen storage is also observed in 85 diabetes [2-4]. Advancements in the modern lifestyle over the last century 86 have contr...