Antifibrotic effects of crocin on thioacetamide-induced liver fibrosis in mice

AbstractLiver fibrosis is a major health concern that results in significant morbidity and mortality. Up-to-date, there is no standard treatment for fibrosis because of its complex pathogenesis. Crocin is one of the main nutraceuticals isolated from the stigma of Crocus sativus with antioxidant and anti-inflammatory activities. The current study aimed at evaluating the potential antifibrotic activity of crocin against thioacetamide (TAA)-induced liver fibrosis in mice as well as the underlying mechanism using silymarin as a reference antifibrotic product. Crocin at two doses (25 and 100mg/kg) significantly ameliorated the rise in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and total bilirubin (TB). Further, the high dose significantly protected against the increase in serum total cholesterol (TC) and triglycerides (TG). These effects were confirmed by light microscopic examinations. Crocin antioxidant activities were confirmed by the observed inhibition of reduced glutathione depletion (GSH), super oxide dismutase (SOD) exhaustion and malondialdehyde (MDA) accumulation in liver tissue. The antifibrotic effects of crocin were explored by assessing fibrosis related gene expression. Administration of crocin (100mg/kg) hampered expression of tumor growth factor-β (TGF-β), α alpha smooth muscle actin (α-SMA) and collagen 1-α expression and significantly raised gene expression of matrix metalloproteinase-2 (MMP-2). Further, it reduced protein expression of nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) as assessed immunohistochemically. These anti-inflammatory effects were confirmed by the observed protein expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Thus, it can be concluded that crocin protects against TAA-induced liver fibrosis in mice. This can be ascribed, at least partly, to its antioxidant and anti-inflammatory effects