Ameliorative Effects of Ficus Carica Leaf Extract on Hepatic Steatosis and Pancreatic Β-Cell Function in Db/Db Diabetic Mice.

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and progressive pancreatic β-cell dysfunction, frequently accompanied by hepatic steatosis. This study investigated the ameliorative effects of Ficus carica leaf extract (FCLE) on hepatic steatosis and pancreatic β-cell function in db/db diabetic mice. Male db/db mice were administered FCLE (250 or 500 mg/kg/day) or vehicle orally for 8 weeks, with age-matched db/+ mice serving as non-diabetic controls. FCLE treatment significantly improved glycemic control, as evidenced by reduced fasting blood glucose (38.5% reduction at 500 mg/kg), HbA1c levels, and enhanced glucose tolerance and insulin sensitivity. Serum lipid profile and liver function markers were significantly improved following FCLE administration. Histological and biochemical analyses revealed that FCLE markedly attenuated hepatic steatosis, reducing hepatic triglyceride content by 41.5% and total cholesterol by 35.8% at the higher dose. FCLE treatment reduced hepatic oxidative stress and modulated the expression of key genes and proteins involved in lipid metabolism, downregulating lipogenic factors (SREBP-1c, FAS, ACC) while upregulating fatty acid oxidation mediators (PPAR-α, CPT-1). In pancreatic tissue, FCLE improved islet morphology, increased β-cell mass by 71.5%, and enhanced the expression of factors critical for β-cell function (PDX1, MAFA, GLUT2, GCK). Moreover, FCLE reduced pancreatic ER stress, inflammation, and β-cell apoptosis. Phytochemical analysis revealed that FCLE contained significant amounts of phenolics (127.5 mg GAE/g) and flavonoids (58.2 mg QE/g), with chlorogenic acid, rutin, and quercetin identified as major bioactive compounds. These findings suggest that FCLE exerts beneficial effects on hepatic steatosis and pancreatic β-cell function in db/db diabetic mice through multiple mechanisms, highlighting its potential as a complementary approach for T2DM management.