Network Pharmacology and In Vivo Experimental Analysis for Validating the Antifibrotic Potential of Punica Granatum Leaves Against Skin Scleroderma: The Role of Oxidative Stress, Inflammation and TGF-β1/Snail 1/p-Smad 3 Signaling Pathway

This study explores the antifibrotic potential of Punica granatum ethanolic leaf extract (PGEL) against skin scleroderma, focusing on oxidative stress, inflammation, and the TGF-β1/Snail 1/p-Smad 3 signaling pathway. In a rat model with 24 subjects, PGEL was administered at doses of 200 and 400 mg/kg, resulting in reduced oxidative stress and inflammation markers, such as IL-17 A, TNF-α, and MMP-9. PGEL also downregulated fibrotic markers like COL1A1 and Snail 1, and decreased TGF-β1 and p-Smad 3 levels, leading to improved dermal thickness and collagen fiber arrangement. The study suggests that PGEL, rich in compounds like ellagic acid and catechin-3-O-gallate, may offer therapeutic benefits for skin fibrosis by targeting inflammation, extracellular matrix production, and oxidative stress.