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.