Ameliorative Effects of Aegle Marmelos Extract on Experimentally Induced Non-Alcoholic Fatty Liver Disease in Wistar Rats

Abstract

Objectives: To investigate the hepatoprotective and metabolic effects of a standardized ethanolic extract of Aegle marmelos Corrêa fruit in a high-fat diet and fructose-induced experimental model of nonalcoholic fatty liver disease in Wistar rats.
Methods: Male Wistar rats (150–180 g) were fed an HFD (60% energy from fat, 5.00 kcal/g) with 10% w/v fructose in drinking water for 16 weeks to induce NAFLD. Following 8 weeks of dietary induction, rats received the ethanolic extract of A. marmelos (250 mg/kg, p.o., once daily) for 8 weeks, with pioglitazone (20 mg/kg, p.o.) as the positive control. The extract, obtained by successive Soxhlet extraction (petroleum ether → ethyl acetate → ethanol) of ripe fruit pulp, was standardized by HPLC. Body mass index, body weight, fasting glucose, insulin, HOMA-IR, serum lipids, hepatic triglycerides, liver function parameters, oxidative stress and antioxidant status, pro-inflammatory cytokines, and hepatic histopathology were assessed.
Results: Chronic HFD/fructose administration produced significant metabolic and hepatic abnormalities, including increased body weight (420.0 g vs. 250.0 g at week 16), body mass index, fasting blood glucose (187.5 ± 3.81 mg/dL vs. 97.5 ± 3.81 mg/dL), insulin and HOMA-IR, dyslipidaemia, hepatic triglyceride accumulation, oxidative stress (elevated MDA with depleted SOD, catalase, GSH), elevated cytokines (TNF-α, IL-1β, IL-6), and hepatocellular injury with vacuolar degeneration and inflammatory infiltration (all p < 0.0001 vs. normal control). A. marmelos treatment significantly attenuated these abnormalities — reducing body weight (360.0 g), BMI (0.7545 ± 0.0088 vs. 0.8698 ± 0.0120), fasting glucose (162.5 ± 3.81 mg/dL), HOMA-IR, hepatic triglycerides, total cholesterol, triglycerides, and LDL-C while raising HDL-C restored hepatic antioxidant defenses and plasma total protein, suppressed pro-inflammatory cytokines, and returned liver histology to no abnormality detected. HPLC confirmed umbelliferone (39.38 ppm), quercetin (19.48 ppm), and aegeline (18.32 ppm) as marker constituents. Pioglitazone produced greater improvements in several glycaemic and metabolic endpoints.
Conclusions: The standardized ethanolic A. marmelos extract exerted broad metabolic, antioxidant, anti-inflammatory, and hepatoprotective effects in HFD/fructose-induced NAFLD, mediated by the synergistic bioactivity of its marker compounds, supporting further investigation of the extract as a potential adjunctive therapeutic candidate for NAFLD and associated metabolic disorders.