Bilirubin-induced liver injury is a severe health issue with inadequate treatment. This study examined whether saffron's Crocin and Crocetin could reduce bile stasis-induced liver injury. This study also investigated how these compounds may affect bile acid metabolism by inhibiting ERK phosphorylation. Network pharmacology analysis and in vitro and in vivo experiments showed that Crocin and Crocetin could affect the ERK signaling pathway, reducing bile acid production and bile stasis-induced liver injury. The study found that Crocin and Crocetin reduced CYP7A1 synthesis by inhibiting ERK signaling pathway phosphorylation and promoting PPARα binding to the promoter. Crocin and Crocetin also increased Mrp3 and Mrp4, which reduced bile acid formation and mitigated bile stasis-induced liver injury. These findings offer new insights into developing novel bile stasis-induced liver injury treatments. All rights reserved, Elsevier.

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