Investigation of the mechanism of action of Shengxuexiaoban Capsules against primary immune thrombocytopenia using network pharmacology and experimental validation

Abstract

BackgroundShengxuexiaoban Capsules (SC) is a classical prescription in traditional Chinese medicine (TCM) and has been clinically adopted in the treatment of primary immune thrombocytopenia (ITP) in China. However, the underlying mechanisms of the actions of SC on ITP remain clear. MethodsA network pharmacology approach was adopted to investigate the underlying molecular mechanism of SC in treating ITP, and the effects of SC on the proliferation, differentiation, and apoptosis of megakaryocyte (MK) and on the ITP animal model were investigated. ResultsNetwork pharmacology analysis found 128 active compounds and 268 targets of these compounds in SC, as well as 221 ITP-related targets. The topological analysis found a central network containing 82 genes, which were significantly associated with the regulation of transcription, cell proliferation, apoptosis processes, the PI3K-AKT signaling pathway, the MAPK signaling pathway, and the ERK1 and ERK2 cascades. It showed that SC increased the proliferation and differentiation of MK, but had no significant impact on MK apoptosis in vivo. The addition of SC increased the gene expression of several potential targets, including STAT3, KDR, CASP3, and TGFB1. In addition, SC administration elevated the protein expression of p-AKT and inhibit the protein expression of p-ERK, but has no impact on the protein expression of p-P38. Moreover, SC could improve haemogram parameters, coagulation indicators, and the proliferation and differentiation of MK in the ITP animal model. ConclusionsThe present study systematically elucidated the underlying mechanisms of SC against ITP and provided an efficient strategy to discover the pharmacological mechanism of TCM. It may strengthen the understanding of SC and facilitate more application of this formula in the treatment of ITP.