Integrated Metabolomics and Network Pharmacology Approach to Explain Possible Action Mechanisms of Xin-Sheng-Hua Granule for Treating Anemia.

Integrated Metabolomics and Network Pharmacology Approach to Explain Possible Action Mechanisms of Xin-Sheng-Hua Granule for Treating Anemia.
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综合代谢组学和网络药理学方法解释新生花颗粒治疗贫血的可能作用机制

DOI:
10.3389/fphar.2018.00165
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发表时间:
2018
影响因子:
5.6
通讯作者:
Duan JA
Duan JA
中科院分区:
医学2区
文献类型:
--
作者:
Pang HQ;Yue SJ;Tang YP;Chen YY;Tan YJ;Cao YJ;Shi XQ;Zhou GS;Kang A;Huang SL;Shi YJ;Sun J;Tang ZS;Duan JA

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新生花颗粒是我国著名的中药方剂,在我国应用已有30多年,主要用于治疗产后疾病,尤其是贫血。然而,XSHG治疗贫血的潜在机制仍不清楚。本研究首次采用UHPLC-QTOF/MS结合多元数据分析等方法对血虚颗粒治疗眼眶出血性贫血大鼠的血浆代谢组学进行分析,探讨血虚颗粒治疗眼眶出血性贫血的可能机制。然后,运用网络药理学的方法构建了XSHG的化合物-靶点-通路网络,对贫血相关信号通路进行了剖析。最后,通过ELISA和Western Blot分析对代谢组学和网络药理学共同途径中的关键靶点进行了实验验证。结果表明,XSHG可能通过调节辅酶A生物合成、鞘脂代谢和HIF-1α途径发挥抗贫血作用,表现为EPOR、F2、COASY水平升高,HIF-1α、SPHK 1和S1 PR 1蛋白表达降低。本研究成功地解释了血塞通颗粒治疗贫血的多药作用机制,并从中药方剂角度探讨了血塞通颗粒治疗贫血的可能策略。
As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than 30 years to treat postpartum diseases, especially anemia. However, underlying therapeutic mechanisms of XSHG for anemia were still unclear. In this study, plasma metabolomics profiling with UHPLC-QTOF/MS and multivariate data method was firstly analyzed to discover the potential regulation mechanisms of XSHG on anemia rats induced by bleeding from the orbit. Afterward, the compound-target-pathway network of XSHG was constructed by the use of network pharmacology, thus anemia-relevant signaling pathways were dissected. Finally, the crucial targets in the shared pathways of metabolomics and network pharmacology were experimentally validated by ELISA and Western Blot analysis. The results showed that XSHG could exert excellent effects on anemia probably through regulating coenzyme A biosynthesis, sphingolipids metabolism and HIF-1α pathways, which was reflected by the increased levels of EPOR, F2, COASY, as well as the reduced protein expression of HIF-1α, SPHK1, and S1PR1. Our work successfully explained the polypharmcological mechanisms underlying the efficiency of XSHG on treating anemia, and meanwhile, it probed into the potential treatment strategies for anemia from TCM prescription.
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影响因子: 16.6
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