Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid.
Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid.
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人参通过逆转谷胱甘肽和胆汁酸紊乱的稳态来减轻环磷酰胺引起的肝毒性
DOI：
10.1038/srep17536
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发表时间：
2015-12-02
影响因子：
4.6
通讯作者：
Li SL
中科院分区：
文献类型：
--
作者：
Zhu H;Long MH;Wu J;Wang MM;Li XY;Shen H;Xu JD;Zhou L;Fang ZJ;Luo Y;Li SL
环磷酰胺（CP）作为一种化疗药物，由于其副作用，特别是肝毒性而受到限制。人参在我国临床上常用于治疗CP，但人参是否以及如何降低肝毒性尚不清楚。本研究探讨了联合用药的保肝作用及机制。研究发现，人参可以改善CP引起的ALP、ALT、ALS、MDA升高和肝脏恶化，增强抗氧化酶的活性和GSH水平。代谢组学研究表明，CP 改变了 33 种内源性代谢物，其中 19 种内源性代谢物在与人参同时服用时通过两个主要途径（即 GSH 代谢和初级胆汁酸合成）被逆转。此外，人参还可以诱导GCLC、GCLM、GS和GST的表达，这些基因与GSH的处理有关，以及FXR、CYP7A1、NTCP和MRP 3的表达，这些基因在胆汁酸的合成和转运中发挥重要作用。此外，与人参合用时，GCLC、GCLM、GS、GST、NTCP 和 MRP3 表达的调控元件之一 NRF 2 上调。总之，人参可以通过调节GSH和胆汁酸紊乱的稳态来减轻CP诱导的肝毒性，这可能是通过诱导肝脏中NRF 2的表达来介导的。
Cyclophosphamide (CP), a chemotherapeutic agent, is restricted due to its side effects, especially hepatotoxicity. Ginseng has often been clinically used with CP in China, but whether and how ginseng reduces the hepatotoxicity is unknown. In this study, the hepatoprotective effects and mechanisms under the combined usage were investigated. It was found that ginseng could ameliorate CP-induced elevations of ALP, ALT, ALS, MDA and hepatic deterioration, enhance antioxidant enzymes’ activities and GSH’s level. Metabolomics study revealed that 33 endogenous metabolites were changed by CP, 19 of which were reversed when ginseng was co-administrated via two main pathways, i.e., GSH metabolism and primary bile acids synthesis. Furthermore, ginseng could induce expression of GCLC, GCLM, GS and GST, which associate with the disposition of GSH and expression of FXR, CYP7A1, NTCP and MRP 3, which play important roles in the synthesis and transport of bile acids. In addition, NRF 2, one of regulatory elements on the expression of GCLC, GCLM, GS, GST, NTCP and MRP3, was up-regulated when ginseng was co-administrated. In conclusion, ginseng could alleviate CP-induced hepatotoxicity via modulating the disordered homeostasis of GSH and bile acid, which might be mediated by inducing the expression of NRF 2 in liver.