Asim Mohammed Eldai Abdalla; Ali Gad Karim Eldai Salih; Heitham Mutwakil Mohammed Mutwakil; Hassan Reda Hassan Elsayed; Abulqasim Mohammed Babiker Sideeg; Tarig Gasim Mohamed Alarabi; Nidal Abubaker Harun & Rihab Mubarak Abbas Osman
Obesity is a growing global health problem linked to insulin resistance (IR), dyslipidemia, and hepatic steatosis. Polyphyllin I (PPI), a steroidal saponin, has exhibited diverse pharmacological effects, but its anti-obesity and hepatoprotective potential remain unclear. This study investigated the anti-obesity, hypolipidemic, anti-hyperglycemic, and hepatoprotective effects of PPI in high- fat diet (HFD)-induced obesity in rats, with a focus on the role of AMP-activated protein kinase (AMPK) activation. Rats were distributed into six groups and treated with either a basal diet, a PPI control, an HFD, an HFD plus PPI (2 or 5 mg/kg), or an HFD plus PPI (5 mg/ kg) plus the AMPK inhibitor, dorsomorphin. Oxidative stress, inflammatory markers, and expression of lipid-regulatory genes were analyzed. Histopathological evaluation of white adipose tissue (WAT) was performed using H&E staining. PPI significantly reduced the body weight, fat mass, fasting glucose, insulin, and lipid profile in HFD-fed rats, independent of food intake. It activated WAT antioxidant enzymes (SOD, GSH, and catalase) and decreased WAT MDA and serum TNF-α and IL-6. PPI increased phosphorylation of AMPK, PPARa, and ACC and downregulated SREBP1 and FAS. These effects were reversed by dorsomorphin. Histopathological analysis revealed marked improvements in adipocyte morphology and reduced inflammatory infiltration in WAT. PPI exerted potent anti-obesity, anti-inflammatory, antioxidant, and hepatoprotective effects through activation of AMPK and modulation of lipid metabolism, supported by histopathological evidence. The results suggest PPI could be a powerful tool in managing obesity and related metabolic health.
KEY WORDS: AMP-activated protein kinase; Saponins; Polyphyllin I; Obesity; Lipogenesis.
ELDAI ABDALLA, A. M.; ELDAI SALIH, A. G. K.; MUTWAKIL, H. M. M.; ELSAYED, H. R. H.; SIDEEG, A. M. B.; ALARABI, T. G. M.; HARUN, N. A. & OSMAN, R. M. A. Molecular and morphological improvements in white adipose tissue mediated by Polyphyllin I in high-fat diet-induced obese. Int. J. Morphol., 44(4):1228-1239, 2026.