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Glycyrrhizic acid rebalances mitochondrial dynamics to mitigate hepatotoxicity induced by triptolideCao, Zhiwen; Liu, Bin; Yan, Lan; Shu, Haiyang; Wang, Lili; Li, Li; Lu, Peipei; He, Xiaojuan; Ouyang, Guilin; Nie, Zhixin; Lu, Aiping; Lu, Cheng
Journal of functional foods, February 2024, 2024-02-00, 2024-02-01, Volume: 113Journal Article
Display omitted •TP-induced hepatotoxicity is associated with mitochondrial dynamic.•TP interferes with mitochondrial dynamics through PKCα and FIS1.•The G&T combination can reduce TP-induced hepatotoxicity.•The G&T combination inhibited the up-regulation of FIS1. Triptolide (TP) has various pharmacological activities, but its hepatotoxicity limits its therapeutic potential. Licorice has been evaluated to harmonize various medicines, and its active ingredient glycyrrhizic acid (GA) has been identified for its detoxification effect. In this study, we demonstrated that the combination of GA and TP (G&T) could mitigate TP-induced hepatotoxicity. To explore TP toxicity and G&T detoxification mechanisms, transcriptomics and proteomics have been utilized. TP was found to promote the expression of PKCα and FIS1, accompanied by an increase in mitochondrial fission. After pretreatment with GA, improvements were observed in TP-induced mitochondrial fission, as well as the expression of active-caspase3, and cytochrome c release. Silencing PKCα and FIS1 has a similar effect to GA on the regulation of mitochondria-dependent apoptosis and mitochondrial fission. In conclusion, PKCα and FIS1-involved mitochondrial dynamic regulation is associated with TP-induced hepatotoxicity. The G&T combination may be an effective strategy for ameliorating TP-induced toxicity.
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