Selenium Nanoparticles Functionalized with Glycosmis pentaphylla Extract Attenuate Hepatic Fibrosis Through Modulation of Oxidative Stress and Anti-Inflammatory Responses
摘要
Hepatic fibrosis, a progressive scarring of liver tissue triggered by persistent oxidative injury and inflammatory cascades, poses a pressing clinical burden with few effective remedies. This investigation evaluates the antifibrotic efficacy of selenium nanoparticles (SeNPs) biosynthesized via a green methodology, employing leaf extract from Glycosmis pentaphylla as a capping agent alongside sodium selenite, yielding stable GPSeNPs enriched with plant-derived bioactive compounds, in a CCl4-induced hepatic fibrosis model in male Swiss albino mice. Liver fibrosis was established through twice-weekly intraperitoneal injections of CCl4 (1 mL/kg) over an 8-week period. Following fibrosis induction, mice received daily oral administration of GPSeNPs at doses of 0.5 or 1.5 mg/kg, or silymarin (50 mg/kg) as a reference standard, for 4 weeks. Treatment with GPSeNPs produced dose-dependent improvements in hepatic function, evidenced by marked reductions in serum activities of ALT, AST, and ALP compared to the CCl4-only group. Histopathological analysis (H&E staining), SEM, and TEM revealed attenuated tissue injury, with reduced collagen accumulation and preserved hepatocyte architecture, alongside decreased hepatic hydroxyproline concentrations. GPSeNPs significantly decreased lipid peroxidation, restored antioxidant enzyme levels (SOD, CAT, and GSH), suppressed pro-inflammatory cytokines (TNF-α, IL-6) and profibrotic TGF-β, and simultaneously elevated anti-inflammatory IL-10. These findings demonstrate that Glycosmis pentaphylla-functionalized SeNPs effectively attenuate CCl4-induced hepatic fibrosis in mice through combined antioxidant, anti-inflammatory, and antifibrotic mechanisms, suggesting their therapeutic promise as a nanofunctionalized natural agent for chronic liver disease.