Multitarget Anti‐Obesity Potential of Baccaurea motleyana Fruit: Insights From Biochemical, Histological, and In Silico Analyses

Obesity, associated with insulin resistance, dyslipidemia, hepatic steatosis, and inflammation, remains a global challenge. This research evaluated the anti‐obesity and hepatoprotective potential of the Baccaurea motleyana fruit ethanol extract (BMF‐EE) in high‐fat‐diet (HFD)‐induced obese rats. Phytochemicals in BMF‐EE were profiled by GC–MS. Male Wistar rats ( n = 5/group) were allocated to a normal diet, HFD control, positive control (silymarin), and BMF‐EE‐treated groups (200 and 400 mg/kg), with treatments administered for 8 weeks following HFD feeding. Body weight, fat mass, serum lipids, glucose homeostasis, oxidative stress markers, inflammatory cytokines, and hepatic histology were evaluated. BMF‐ME reduced body weight gain ( p < 0.01) and epididymal fat ( p < 0.05) compared to HFD controls. Serum triglycerides (↓32%, p < 0.01), total cholesterol (↓28%, p < 0.05), and LDL‐C (↓35%, p < 0.01) were significantly decreased, while HDL‐C increased (↑22%, p < 0.05). Fasting glucose (↓27%, p < 0.01), insulin (↓25%, p < 0.05), and HOMA‐IR (↓31%, p < 0.01) levels were significantly reduced, accompanied by better outcomes on the OGTT and IPITT tests. Hepatic MDA was decreased significantly ( p < 0.01), while SOD, CAT, and GPx were restored significantly ( p < 0.05). TNF‐α and IL‐6 levels were also markedly suppressed ( p < 0.05). Molecular docking showed strong binding of BMF‐EE metabolites to HMG‐CoA reductase. BMF‐EE improves obesity‐related metabolic disturbances through lipid regulation, glucose sensitization, and antioxidative and anti‐inflammatory effects, providing evidence for natural interventions for obesity. Further studies should identify active compounds and their mechanisms.