Exploring the therapeutic mechanism of Miao nationality medicine Qijiao Shengbai capsule on leukopenia based on multi-omics, network pharmacology and experimental verification.

INTRODUCTION

Leukopenia is caused by numerous factors, and modern drug therapies have obvious side effects, Qijiao Shengbai Capsule (QJSB) is a compound prescription developed from Miao medicine, widely used in clinical treatment of leukopenia. However, its mechanism of action for treating leukopenia remains unclear.

OBJECTIVES

This study aims to investigate the active ingredients, effects and underlying mechanism of QJSB on leukopenia.

MATERIALS AND

METHODS

In this study, the chemical components of QJSB and serum constituents were identified using UPLC-Q-Qrbitrap HRMS technology. The potential anti-leukopenia mechanism and crucial components of QJSB was deciphered using combined approaches of transcriptomic analysis and network pharmacology analysis. Finally, the expression of key targets and the intervene effects of QJSB in the cyclophosphamide-induced leukopenia model of rats was verified by in vivo experiments.

RESULTS

In total, 51 and 58 chemical components were identified from QJSB and serum respectively. The network pharmacology analysis indicated that the key components of QJSB was genistein, quercetin, 5,6,7-trimethoxyisoflavone, carbacyclin, linoleic acid, and caffeic acid, the key targets were PTPN11, LCK, STAT3, GRB2, FYN, SRC, PIK3R1, LYN, EGFR, PIK3CA, and the key pathways were PI3K-Akt, lipid and atherosclerosis, JAK-STAT, FoxO, and linoleic acid metabolism. Transcriptomics analysis revealed that 1171 genes were down-regulated and 382 genes were up-regulated by QJSB compared with model group. KEGG pathway enrichment analysis indicated that the PI3K-AKT signaling pathway is closely related to leukopenia. Animal experiments demonstrated that QJSB and its active components effectively increased serum levels of hematopoietic and immune-related cytokines, improved thymus index, spleen index, and bone marrow nucleated cell count in model rats through regulating PI3K-AKT signaling pathway and downstream transcription factors mTOR and FOXO3A.

CONCLUSION

Our research demonstrated for the first time that genistein, quercetin, and caffeic acid is the key active components of QJSB and this miao nationality medicine can treat leukopenia through regulating the PI3K-AKT-mTOR/FoxO3a signaling axis.