Green-Synthesized Rutin-Capped Gold Nanoparticles Attenuate Experimental Liver Fibrosis by Targeting Oxidative Stress and TGF-β Signaling

Liver fibrosis can develop after sustained oxidative stress and inflammatory signaling and transforming growth factor-β (TGF-β) is a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but with limited bioavailability, which impedes therapeutic efficacy. This study investigated the hepatoprotective potential of rutin-phytoreduced gold nanoparticles (RuAuNPs) in a thioacetamide (TAA)-induced rat model of liver fibrosis. RuAuNPs were spherical, 18nm diameter (transmission electron microscopy -TEM) and exhibited SPR peak at 523nm (UV–Vis spectroscopy). Following liver fibrosis induction, animals were treated with free rutin or RuAuNPs. Oxidative stress (spectrophotometry, fluorimetry), inflammation (ELISA) and liver morphology (histopathology, TEM) were evaluated. TAA induced hepatic injury and fibrotic remodeling, associated with elevated TGF-β expression, oxidative stress, and inflammation. Free rutin showed limited recovery of liver parameters. RuAuNP treatment significantly improved hepatic histology and ultrastructure, reduced TGF-β and pro-inflammatory cytokine levels (TNFα, IL1β, IL6), decreased oxidative stress damage (lipid peroxidation), restored glutathione redox balance, and enhanced superoxide dismutase activity. Improvement in the AST/ALT ratio suggested early functional recovery, despite persistent aminotransferase elevation. Overall, RuAuNPs enhanced rutin’s antifibrotic and hepatoprotective effects by targeting oxidative and inflammatory pathways and can represent an effective delivery system for rutin in liver fibrosis therapy.