Mechanism of herb pair containing Astragali Radix and Spatholobi Caulis in the treatment of myelosuppression based on network pharmacology and experimental investigation.

ETHNOPHARMACOLOGICAL RELEVANCE:The Astragali Radix and Spatholobi Caulis herb pair (ARSC) is one of the most commonly used herbal combinations for bone marrow suppression. According to traditional Chinese medicine, Astragali Radix strengthens the spleen and replenishes qi, while Spatholobi Caulis is a hematinic agent that promotes blood circulation and enrichment. The compatibility of the two helps the body to tonify the spleen and kidneys and compensate for visceral deficiencies. However, the multi-target mechanism of ARSC in bone marrow suppression has remained largely unknown. AIM OF THE STUDY:The aim of this study is to explore the key targets and signaling pathways of the traditional Chinese herbal pair ARSC for the treatment of bone marrow suppression. MATERIALS AND METHODS:The active components of ARSC and targets for myelosuppression were screened using network databases. Cytoscape 3.8.0 was used to construct compound-target, compound-disease-target and protein-protein interaction (PPI) networks. Go-function and pathway enrichment analyses were performed to explore the potential mechanism. In vivo animal experiments were conducted to verify the molecular mechanisms. RESULTS:The 36 active compounds were identified from the ARSC, and a total of 108 genes involved in myelosuppression were screened. VEGFA, IL6, TNF, JUN, STAT3, PTGS2, CASP3 and MMP9 genes were identified as potential drug targets in the PPI network analyzed by CytoHubba. Enrichment analysis indicated that ARSC may treat myelosuppression through various biological processes, such as apoptosis, TNF-α signaling pathway via NF-κB, PI3K/AKT/mTOR signaling pathway, IL6/JAK/STAT3 signaling pathway, P53 signaling pathway and G2/M checkpoint signaling pathway. The results of the experiment showed that the aqueous extract of ARSC significantly alleviated myelosuppression, reduced the apoptosis rate of bone marrow cells, upregulated the mRNA expression levels of TNF-α, IL-6 and VEGF, and promoted NF-κB phosphorylation in myelosuppressed mice. CONCLUSIONS:This study identified the active components and relevant mechanisms of ARSC in the treatment of myelosuppression. Our findings predicted that ARSC could treat bone marrow suppression through multiple components, multiple targets and multiple pathways. Pharmacological experiments showed that ARSC alleviated fluorouracil-induced myelosuppression by reducing the apoptosis rate of bone marrow cells and regulating the TNF-α/NF-κB signaling pathway.