Abstract

Qishen Yiqi formula (QSYQ) has the effect of tonifying Qi and promoting blood circulation, which is widely used to treat the cardiovascular diseases with Qi deficiency and blood stasis syndrome. However, the mechanism of QSYQ to tonify Qi and promote blood circulation is rarely reported at molecular or systems level. This study aimed to elucidate the mechanism of QSYQ based on the protein interaction network (PIN) analysis. The targets' information of the active components was obtained from ChEMBL and STITCH databases and was further used to search against protein-protein interactions by String database. Next, the PINs of QSYQ were constructed by Cytoscape and were analyzed by gene ontology enrichment analysis based on Markov Cluster algorithm. Finally, based on the topological parameters, the properties of scale-free, small world, and modularity of the QSYQ's PINs were analyzed. And based on function modules, the mechanism of QSYQ was elucidated. The results indicated that Qi-tonifying efficacy of QSYQ may be partly attributed to the regulation of amino acid metabolism, carbohydrate metabolism, lipid metabolism, and cAMP metabolism, while QSYQ improves the blood stasis through the regulation of blood coagulation and cardiac muscle contraction. Meanwhile, the “synergy” of formula compatibility was also illuminated.

Highlights

  • Qishen Yiqi formula (QSYQ), consisting of Radix Salvia miltiorrhiza, Panax notoginseng, Dalbergia odorifera, and Astragalus membranaceus, has the effect of tonifying Qi, promoting blood circulation and relieving pain, and it has been widely used to treat the cardiovascular diseases with Qi deficiency and blood stasis syndrome [1, 2]

  • Tanshinone IIA, cryptotanshinone, salvianolic acid A, salvianolic acid B, tanshinol, and protocatechuic aldehyde are from Salvia miltiorrhiza which is a classical traditional Chinese medicine (TCM) which can promote blood circulation and remove blood stasis with 1000 years of clinical application [27]

  • It has been demonstrated that Salvia miltiorrhiza can reduce the area of cerebral infarct of ischemia-reperfusion injury rats which results from blood stasis [28]

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Summary

Introduction

Qishen Yiqi formula (QSYQ), consisting of Radix Salvia miltiorrhiza, Panax notoginseng, Dalbergia odorifera, and Astragalus membranaceus, has the effect of tonifying Qi, promoting blood circulation and relieving pain, and it has been widely used to treat the cardiovascular diseases with Qi deficiency and blood stasis syndrome [1, 2]. The research of Cui et al [7] had shown that, by detecting clinical indexes which included the right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (SV), and right ventricular ejection fraction (RVEF), QSYQ could significantly improve the right heart function on patients undergoing valve replacement. The findings of these studies explain the action mechanism of QSYQ to some extent, but the further study of QSYQ is still to be done. The mechanism of QSYQ was illuminated by the network analysis approach which has the advantage of evaluating TCM’s pharmacological effect as a whole unity at molecular level [8, 9]

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