Effects of Dillenia indica L. fruit extract on hepatic Cyp7a1 gene expression in a rat model of streptozotocin-induced diabetes-associated dyslipidemia

Background Dillenia indica fruit has long been documented to exert multiple health benefits, including antidiabetic and antidyslipidemic activities. Objective To investigate whether modulation of hepatic Cyp7a1 gene expression mediates the antidiabetic and antidyslipidemic effects of an 80% methanolic extract of D. indica fruit (DiME). Methods Phytochemical profiling of DiME was performed using qualitative assays and gas chromatography-tandem mass spectrometry (GC–MS/MS). Diabetes was induced in 48-hour-old rat pups via a single intraperitoneal injection of streptozotocin (90 mg/kg). After 3 months, 18 adult rats were confirmed as type 2 diabetes mellitus (T2DM) models using the oral glucose tolerance test (OGTT). Dyslipidemia was subsequently induced by feeding a high-cholesterol diet supplemented with 2% cholesterol and 1% cholic acid for 4 weeks. The rats were then randomly divided into four groups ( n = 6 per group) and received respective treatments for 28 consecutive days. Blood samples were collected under halothane anesthesia. Therapeutic efficacy was evaluated by measuring fasting serum glucose (FSG), insulin, homeostatic model assessment (HOMA) indices (HOMA-B, HOMA-S, HOMA-IR), lipid profiles (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol), and liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT)). Mechanistic studies included measurement of serum superoxide dismutase (SOD) activity, pancreatic histopathological examination, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of hepatic Cyp7a1 gene expression, and in silico molecular docking. Results DiME was rich in terpenoids, phenols, and fatty acids. In vivo , DiME treatment significantly reduced FSG ( P < 0.01) and markedly improved lipid profiles by decreasing serum TG, TC, and LDL cholesterol, while increasing HDL cholesterol ( P < 0.05). This was accompanied by a 93% elevation in serum insulin levels ( P < 0.001) and significant improvements in pancreatic β-cell function (HOMA-B) and insulin sensitivity (HOMA-S). Histological analysis confirmed preservation of pancreatic islet integrity. DiME also ameliorated oxidative stress by increasing serum SOD activity and exerted hepatoprotective effects by reducing elevated serum AST and ALT levels. Mechanistically, DiME treatment induced an approximately 3-fold upregulation of hepatic Cyp7a1 gene expression. Conclusion These findings indicate that DiME exerts its therapeutic effects via a dual mechanism by enhancing pancreatic insulin secretion and peripheral insulin sensitivity, and upregulating hepatic Cyp7a1 expression to promote cholesterol catabolism.