The Biochemical Role of Bitter Melon ( Momordica charantia L.) Aqueous Extract in Regulating Hepatic Gluconeogenesis in Rats Fed Ketogenic Diet

ABSTRACT The ketogenic diet (KD) has been suggested as a useful lifestyle intervention for metabolic syndrome; however, its long‐term metabolic effects remain debated. This study evaluated the biochemical impact of supplementing KD‐fed rats with a diluted aqueous extract of Bitter Melon (BM) on the regulation of hepatic gluconeogenesis. Thirty‐two male rats were divided into four groups: G1 (Control), G2 (KD), G3 (BM extract, 1.5 g/kg body weight), and G4 (KD + BM extract, 1.5 g/kg body weight). Serum and liver samples were analyzed for biochemical parameters. KD reduced glucose, insulin, triglycerides (TG), Free Fatty Acids (FFA), glycogen, pyruvate carboxylase, and PEPCK, while elevating cholesterol (+34%), lactate, and ketone bodies ( p < 0.05). BM supplementation partially restored glucose (+15%), insulin, TG, FFA, glycogen, and enzyme activity, while lowering cholesterol (−14%), lactate (−16%), and ketone bodies (−27%) ( p < 0.05). Histological analysis confirmed improved liver architecture in BM‐treated groups. BM aqueous extract counteracts KD‐induced metabolic disturbances, improving glucose and lipid homeostasis and supporting its role as a safe adjunct to KD for long‐term metabolic management.