AUTHOR=Jia Guanfei , Jiang Xiuxing , Li Zhiqiang , Ding Xin , Lei Ling , Xu Shuangnian , Gao Ning 

TITLE=Decoding the Mechanism of Shen Qi Sha Bai Decoction in Treating Acute Myeloid Leukemia Based on Network Pharmacology and Molecular Docking

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.796757

DOI=10.3389/fcell.2021.796757

ISSN=2296-634X

ABSTRACT=Traditional Chinese Medicine (TCM) has been shown to be efficacious in the treatment of leukemia for thousands of years. It has been shown that Shen Qi Sha Bai Decoction (SQSBD) has been extensively used in the treatment of acute myeloid leukemia (AML). However, the mechanism of SQSBD in treating AML remains unclear. In this study, network pharmacology was used to analyze the potential active ingredients and explore molecular mechanism of SQSBD in treating AML. A total of 268 active ingredients were identified from SQSBD, among which 9 key ingredients (Quercetin, luteolin, kaempferol, licochalcone A, formononetin, wogonin, β-sitosterol, oroxylin A, naringenin, and baicalein) were hit by the 6 hub targets (CDK1, MAPK1, JUN, PCNA, HSB1, STAT3) associated with leukemia. Molecular docking showed that two core active ingredients, quercetin and licochalcone A, exhibited the highest ingredient-like properties (DL), and could bind well to CDK1 and MAPK1 protein. The experimental validation of these two ingredients showed that quercetin inhibited cell growth through CDK1 dephosphorylation-mediated cell cycle arrest at G2/M phase in human AML U937 and HL60 cells, and licochalcone A induced cell differentiation in these leukemia cells via activation of MAPK1 and upregulation of CD11b. All these results indicate that SQSBD is effective in the treatment of AML, and quercetin and licochalcone A are the major candidate compounds for AML treatment.