iTRAQ Quantitative Proteomic Analysis of Different Expressed Proteins and Signal Pathways in Bakuchiol-Induced Hepatotoxicity

Abstract

Bakuchiol (BAK) is an abundant natural compound. BAK has been reported to have several biological activities such as anticancer, antiaging, anti-inflammatory, and prevention of bone loss. However, it causes hepatotoxicity, the mechanism of which is not known. In this study, we explored the mechanism of BAK hepatotoxicity by treating rats with 52.5 mg/kg and 262.5 mg/kg of BAK, administered continuously for 6 weeks. We examined the liver pathology and biochemical composition of bile to determine toxicity. Mechanisms of BAK hepatotoxicity were analyzed based on relative and absolute quantification (iTRAQ) protein equivalent signatures and validated in vitro using LO2 cells. iTRAQ analysis revealed 281 differentially expressed proteins (DEPs) in liver tissue of the BAK-treated group, of which 215 were upregulated, and 66 were downregulated. GO and KEGG enrichment analysis revealed that bile secretion, lipid metabolism, and cytochrome P450 signaling pathways were enriched in DEPs. Among them, peroxisome proliferator-activated receptor α (PPARα), farnesoid X receptor (FXR), and cholesterol 7α-hydroxylase (CYP7a1) were closely associated with the development and progression of BAK-induced hepatic metabolic dysfunction and abnormal bile metabolism. This study shows that BAK can induce hepatotoxicity through multiple signaling pathways.

Dual effects of Psoraleae Fructus on the liver: hepatoprotection or hepatoxicity?

“…BAK administered at doses of 52.5 and 262.6 mg/kg for 6 weeks can also induce DIC, leading to decreased expression of CYP7A1, HMG-CoA reductase, PPARα, and SREBP-2 [78] . iTRAQ results confirmed the close association of PPARα, FXR, and CYP7A1 with the development and progression of BAK-induced cholestatic hepatoxicity [79] .…”