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

Guanfei Jia; Xiuxing Jiang; Zhiqiang Li; Xin Ding; Ling Lei; Shuangnian Xu; Ning Gao

doi:10.3389/fcell.2021.796757

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

Front Cell Dev Biol. 2021 Dec 20:9:796757. doi: 10.3389/fcell.2021.796757. eCollection 2021.

Authors

Guanfei Jia¹, Xiuxing Jiang¹, Zhiqiang Li¹, Xin Ding¹, Ling Lei¹, Shuangnian Xu², Ning Gao^{1

3}

Affiliations

¹ College of Pharmacy, Army Medical University, Chongqing, China.
² Department of Hematology, Southwest Hospital, Army Medical University, Chongqing, China.
³ Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.

Abstract

Traditional Chinese Medicine (TCM) has been shown to be efficacious in treating 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, we employed network pharmacology to analyze the potential active components and elucidate molecular mechanism of SQSBD in treating AML. A total of 268 active components were identified from SQSBD, among which 9 key components (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 components, quercetin and licochalcone A, exhibited the highest component-like properties (DL), and could bind well to CDK1 and MAPK1 protein. The experimental validation of these two components 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.

Keywords: KEGG; acute myeloid leukemia; go; molecular docking; network pharmacology.