Background Flacourtia inermis Roxb. (Salicaceae) is an underutilized edible fruit known for its antioxidant-rich bioactive compounds. This study explores the antiobesity potential of F. inermis ethanolic fruit extract (FF2) in a high-fat diet (HFD) induced obesity model using Wistar albino rats. Materials and Methods Wistar albino rats were randomly assigned into five groups (n = 6). Group 1 served as the normal control and received a normal diet (ND), while Groups II–V were induced with obesity by being fed an HFD for 10 weeks. Group II acted as the obese control, receiving 100% HFD throughout the study. Groups III, IV, and V also received HFD throughout the study but were supplemented with Orlistat (30 mg/kg b.w), and FF2 extract at doses of 200 mg/kg, and 400 mg/kg, respectively, from week 11 until week 15. Treatment impact of FF2 on body weight, body mass index (BMI), serum lipid levels, glucose levels, liver function parameters, and histopathological evaluations of liver and adipose tissue were investigated. Results The study unveiled that F. inermis fruits exerted potent antiobesity effects, with FF2 treatment (at 200 mg/kg and 400 mg/kg) substantially decreasing body weight gain and BMI in comparison to the HFD group. Supplementation of FF2 alongside an HFD reduced body weight gain, glucose levels, and serum lipid profile. Both doses of FF2 counteracted the adverse effects induced by HFD, with lower triglycerides (TG), total cholesterol, and LDL cholesterol levels, and higher HDL cholesterol levels in the treated groups compared to the positive control. Additionally, FF2 extract showed dose-dependent improvements in serum lipid and glucose levels, as well as, hepatic profile, indicated by decreased AST, ALP, and ALT levels, suggesting potential benefits in managing dyslipidemia, hyperglycemia, and liver health associated with obesity. Histological examination of white adipose tissue provided further evidence of the antiobesity effect. Conclusion The study highlights FF2’s therapeutic potential in managing obesity and associated metabolic disorders. Further investigations into FF2’s mechanisms and clinical application are essential for its development as an antiobesity therapeutic agent in functional food formulations.
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