Protective effects of cirsimaritin in mice model of alcohol-induced liver disease

Alcoholic liver disease (ALD) is the result of excessive alcohol intake that manifests in the initial stage as fatty liver, resulting in alcoholic hepatitis, fibrosis, and cirrhosis. This study investigates the role of cirsimaritin on hepatic regeneration, protection, and fibrosis in in vivo and in vitro model of ALD. In vivo model of ALD was developed with chronic-plus-binge ethanol feeding in C57B6 mice. Cirsimaritin was administered intraperitoneally at a dose of 1 µg/g body weight. An in vitro model was established by treating HepG2 cells with 0.1% ethanol to mimic alcoholic liver injury and treated with different cirsimaritin concentrations (500 ng and 1000 ng/mL). mRNA and protein expression levels of fibrotic, regenerative, hepatoprotective, and inflammatory genes were analysed. The molecular docking of cirsimaritin was performed against important signalling molecules using AutoDock 4.2.2. Our results suggested that there is an increase in the ratio of AST/ALT levels predictive of ethanol induced liver damage in the ethanol-fed group, which was abrogated with cirsimaritin administration. Cirsimaritin treatment also reduced the severity of liver injury in the ALD in-vivo model by inhibiting hepatic steatosis, inflammation, and liver fibrosis. We observed liver regeneration in the ethanol-treated mice treated with cirsimaritin. Cirsimaritin showed significant binding affinities ranging from − 4.46 to − 8.46 kcal/mol, with the strongest interaction observed for ERK1 (− 8.46 kcal/mol) followed closely by p38 MAPK (− 8.39 kcal/mol). These results demonstrated that cirsimaritin showed preventive action by modulating the fibrotic, inflammatory, hepatoprotective and regenerative cascades.