Visnagin Attenuates Thioacetamide‐Induced Liver Injury and Fibrosis Through the Modulation of TLR4‐Mediated Inflammation and Downregulation of TGF‐β/α‐SMA‐Driven Fibrogenesis

Liver fibrosis represents an abnormal wound‐healing response to chronic hepatic injury. It is characterized by the excessive production and deposition of extracellular matrix components, ultimately resulting in the formation of a fibrotic scar. Visnagin, a phytochemical, has antioxidants and anti‐inflammatory activity and modulates apoptosis; however, the role of visnagin in liver fibrosis has not been previously explored. Herein, we have induced liver fibrosis using thioacetamide (TAA; 200 mg/kg) through the intraperitoneal (i.p.) route every third day for 8 weeks in Sprague Dawley rats. Visnagin (5 and 10 mg/kg) co‐treatment was given via the i.p . route every day for 8 weeks. At the end of the visnagin intervention, various biochemical, oxidative stress parameters, histopathological assessments, and quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) analyses were performed. Visnagin administration resulted in a significant decrease in the liver‐to‐body weight ratio and liver injury markers, including alanine transaminase, aspartate aminotransferase, and alkaline phosphatase. Additionally, visnagin attenuated TAA‐induced oxidative stress by restoring levels of malondialdehyde, nitrite, and superoxide dismutase. Histopathological assessments confirmed the hepatoprotective effects of visnagin against TAA‐induced liver injury, as evidenced by a reduction in hepatocyte damage and collagen deposition. Further, at a molecular level, visnagin treatment reduces the expression of caspase‐3 and genes related to inflammation (TLR4, TNF‐α, IL‐6, NLRP3) and fibrosis (α‐SMA, Col1A1, TGF‐β, MMP9, and TIMP1) in TAA‐treated rats.