Elucidating the hepatoprotective mechanisms of cholic acid against CCl4-Induced acute liver injury: A transcriptomic and metabolomic study

Ethnopharmacological relevance Cholic acid (CA) is one of the main active ingredients in Calculus Bovis, a traditional Chinese medicine, which helps to regulate the heart and liver meridians, clearing the heart, opening the mouth, cooling the liver and calming the wind. However, the molecular mechanism of its liver protective effect is still unclear. Aim of the study Growing attention has been directed towards traditional Chinese medicine (TCM), particularly Calculus Bovis, as a potential solution for liver protection. Despite this interest, a comprehensive understanding of its hepatoprotective mechanisms remains lacking. This research seeks to explore the potential protective properties of cholic acid (CA) against CCl4-induced acute liver injury (ALI) in mice, while also examining the mechanisms involved. Materials and methods In the experiment, a mouse model was employed to ALI using CCl4, and the potential therapeutic effects of orally administered CA at varying doses (15, 30, and 60 mg/kg) were assessed. The study employed a multi-faceted approach, integrating liver transcriptomics with serum metabolomics, and conducting thorough analyses of serum biochemical markers and liver histopathological sections. Results Oral CA administration markedly reduced the organ indices of the liver, spleen, and thymus in comparison with the model group. It also elevated the expression of superoxide dismutase (SOD) in serum while diminishing the concentrations of ALT, AST, MDA, IL-6, and TNF-α. Moreover, CA ameliorated the pathological damage induced by CCl4. Integrated metabolomic and transcriptomic analyses indicated that the hepatoprotective action of CA on ALI is mediated through the modulation of lipid metabolic pathways—specifically, metabolisms of glycerophospholipid, arachidonic acid, as well as linoleic acid—and by altering the expression of genes such as Ptgr1, PLpp1, Tbxas1, and Cyp2c37. Conclusions The current investigation offers insights into the hepatoprotective mechanisms by which CA mitigates ALI caused by CCl4 exposure, thus supporting the further evaluation and development of CA-based therapeutics for ALI.