Abstract
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.
Highlights
Anemia, one of the most common diseases in obstetrics, could cause severe maternal and fetal complications, including preterm birth and placental mesenchymal dysplasia (Mousa et al, 2014)
To evaluate whether these constituents could be detected in the rat plasma after oral administration of Xin-Sheng-Hua granule (XSHG) prescriptions, 43 ingredients were characterized by UHPLC-QTOF-MS, which suggested that these screening compounds were believable to be applied in the network pharmacology analysis
The crucial targets of shared pathways were firstly selected from the constructed network: coenzyme A biosynthesis (ACSS1 and COASY), cysteine and methionine metabolism (CBS and AHCY), and sphingolipid signaling pathway (SPHK1 and S1PR1)
Summary
One of the most common diseases in obstetrics, could cause severe maternal and fetal complications, including preterm birth and placental mesenchymal dysplasia (Mousa et al, 2014). The available therapeutic drugs and their therapeutic effects were limited, and some of them even caused obvious side effects (Milman, 2012; Tunçalp et al, 2013). For these reasons, the discoveries of potential strategies for treating anemia could have a positive effect on maternal as well as fetal outcomes. In the past few decades, Xin-Sheng-Hua granule (XSHG) has been widely applied for the treatment of anemiarelated diseases in China, especially for the anemia caused by postpartum hemorrhage, whose prescription is the boiled water extraction followed by seven common herbs, Angelica sinensis (Oliv.) Diels (ASD; Danggui), Leonurus artemisia (Laur.) S. Up to date, the action mechanism for treating anemia of XSHG remained poorly understood
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