AUTHOR=Pang Han-Qing , Yue Shi-Jun , Tang Yu-Ping , Chen Yan-Yan , Tan Ya-Jie , Cao Yu-Jie , Shi Xu-Qin , Zhou Gui-Sheng , Kang An , Huang Sheng-Liang , Shi Ya-Jun , Sun Jing , Tang Zhi-Shu , Duan Jin-Ao TITLE=Integrated Metabolomics and Network Pharmacology Approach to Explain Possible Action Mechanisms of Xin-Sheng-Hua Granule for Treating Anemia JOURNAL=Frontiers in Pharmacology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00165 DOI=10.3389/fphar.2018.00165 ISSN=1663-9812 ABSTRACT=As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than thirty years to treat postpartum diseases, especially anaemia. However, the underlying therapeutic mechanisms of XSHG for anaemia were still unclear. In this study, plasma metabolomics profiling for anaemia was firstly analyzed by UHPLC-QTOF/MS and multivariate data method. Using network pharmacology, the compound-target-pathway network of XSHG was constructed, so as to dissect anaemia-relevant signaling pathways. 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 anaemia probably through regulating coenzyme A biosynthesis, sphingolipids metabolism, and HIF-1a signaling pathways, which was reflected by the increased levels of EPOR, F2, COASY, and the reduced protein expression of HIF-1a, SPHK1, and S1PR1. Our work successfully explained the polypharmcological mechanisms underlying the efficiency of XSHG on treating anaemia, and meanwhile, probed into the potential treatment strategies for anaemia from TCM prescription.