<br>Bavachin 联合 epimedin B 在免疫应激条件下诱导特异质性肝损伤,Chemico-Biological Interactions

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Bavachin 联合 epimedin B 在免疫应激条件下诱导特异质性肝损伤
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2023-10-20 , DOI: 10.1016/j.cbi.2023.110774
Mengmeng Lin ₁ , Yingying Li ₁ , Bo Cao ₁ , Jing Xu ₁ , Yujun Zhang ₁ , Guohui Li ₁ , Xiaohe Xiao ₂ , Chunyu Li ₁

Affiliation

含有淫羊藿（EF）和补骨脂（PF）的中成药制剂导致特异质药物性肝损伤（IDILI）的报道受到广泛关注。先前的研究表明，bavachin 和 epimedin B（两种源自 EF 和 PF 的活性成分）是与 IDILI 相关的潜在成分，但其潜在机制仍不清楚。我们在 TNF α介导的免疫应激条件下评估了 bavachin 和 epimedin B 诱导的 IDILI，并使用脂质组学和多变量统计分析生成肝脏脂质代谢谱。接下来，我们应用转录组学来识别转录水平上的差异基因表达。我们的结果表明，在免疫应激条件下共同暴露于 bavachin、epimedin B 导致明显的肝损伤。我们研究中筛选的差异代谢物与肝脏的免疫稳态密切相关。发现 16 个差异表达基因，Zc3h6 和 R3hdml 上调，而 Sumo2 、 Cd74 、 Banp 、 Oas3 、 Oas2 、 Gbp8 、 Slfn8、 Gbp2b 、 Serpina3g 、 Zbtb40 、 H2-ab1 、 Osgin1 、 Tgtp1 和 Hspa1b 均下调。这些差异表达基因与代谢过程和免疫系统过程的生物过程有关。进一步的综合分析表明，bavachin 与 epimedin B 联合影响的基因不仅与免疫系统过程有关，还与脂质代谢有关。最终，这导致肝脏免疫微环境失衡，并可能导致观察到的肝损伤。

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Bavachin combined with epimedin B induce idiosyncratic liver injury under immunological stress conditions

Reports on Chinese patent medicines preparations containing Epimedii Folium (EF) and Psoraleae Fructus (PF) resulting in idiosyncratic drug-induced liver injury (IDILI) have received widespread attention. Previous studies have shown that bavachin and epimedin B—two active ingredients derived from both EF and PF—are potential components associated with IDILI, but the underlying mechanism remains unclear. We evaluated bavachin and epimedin B-induced IDILI under TNF-α-mediated immunological stress conditions and generated liver lipid metabolism profiles using lipidomics and multivariate statistical analysis. We next applied transcriptomics to identify the differential gene expression on the transcription level. Our results showed that co-exposure to bavachin, epimedin B under immunological stress conditions resulted in obvious liver injury. The differential metabolites screened in our study were closely related to the immune homeostasis of the liver. Sixteen differentially expressed genes were found, Zc3h6 and R3hdml were upregulated, while Sumo2, Cd74, Banp, Oas3, Oas2, Gbp8, Slfn8, Gbp2b, Serpina3g, Zbtb40, H2-Ab1, Osgin1, Tgtp1 and Hspa1b were all downregulated. These differentially expressed genes were associated with biological processes concerning metabolic process and immune system process. Further integrative analysis indicated that bavachin combined with epimedin B affected genes that were not only related to immune system processes, but also to lipid metabolism. Ultimately, this led to an imbalance in the immune microenvironment in the liver and may have contributed to the observed liver injury.

更新日期：2023-10-20

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