Targeting NF-kappa B/proinflammatory cytokines/ TGF-β/ TIMP-1 pathway by crocin enhances recovery from hepatic fibrosis in rats

BACKGROUND: Liver fibrosis is a dynamic and potentially reversible process until irreversible structural changes occur. This study evaluated the curative effect of crocin on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in rats and explored the underlying mechanisms. METHODS: Thirty male rats were allocated into three groups: a control group treated subcutaneously (SC) with corn oil for 8 weeks followed by intraperitoneal (IP) saline for 2 weeks; a spontaneous recovery group (CCl₄-SC for 8 weeks followed by saline IP for 2 weeks); and a crocin recovery group (CCl₄-SC for 8 weeks followed by crocin 100 mg/kg/day IP for 2 weeks). Liver function tests, fibrosis biomarkers, collagen deposition, inflammatory mediators, oxidative stress indices, and the gene expression of collagen I and α-SMA were assessed using ELISA, spectrophotometry, or qRT-PCR. RESULTS: Crocin significantly improved liver function and reduced fibrosis markers (hyaluronic acid, laminin, PCIII, hydroxyproline, TGF-β, TIMP-1). Furthermore, it downregulated collagen I and α-SMA expression and suppressed NF-κB mediated inflammatory cytokines (TNF-α, IL-1β, NO). It also enhanced antioxidant defenses (GSH, SOD, catalase, GSH-Px) compared with the spontaneous recovery group. CONCLUSION: Crocin exerts a promising curative effect against CCl₄-induced hepatic fibrosis in rats by suppressing NF-κB driven inflammation and profibrogenic mediators, thereby limiting collagen deposition.