Ursolic acid induces apoptosis and pyroptosis in Reh cells by upregulating of the JNK signalling pathway based on network pharmacology and experimental validation

Ying Luo; Jing Xiang; Shuangyang Tang; Shiting Huang; Yishan Zhou; Haiyan Shen

Heliyon (Dec 2023)

Ursolic acid induces apoptosis and pyroptosis in Reh cells by upregulating of the JNK signalling pathway based on network pharmacology and experimental validation

Ying Luo,
Jing Xiang,
Shuangyang Tang,
Shiting Huang,
Yishan Zhou,
Haiyan Shen

Affiliations

Ying Luo: Institute of Biochemistry and Molecular Biology, The Key Laboratory of Environment and Critical Human Diseases Prevention of the Education Department of Hunan Province, Hengyang Medical College, University of South China, Hengyang 421001, China
Jing Xiang: Institute of Biochemistry and Molecular Biology, The Key Laboratory of Environment and Critical Human Diseases Prevention of the Education Department of Hunan Province, Hengyang Medical College, University of South China, Hengyang 421001, China
Shuangyang Tang: Institute of Biochemistry and Molecular Biology, The Key Laboratory of Environment and Critical Human Diseases Prevention of the Education Department of Hunan Province, Hengyang Medical College, University of South China, Hengyang 421001, China
Shiting Huang: Institute of Biochemistry and Molecular Biology, The Key Laboratory of Environment and Critical Human Diseases Prevention of the Education Department of Hunan Province, Hengyang Medical College, University of South China, Hengyang 421001, China
Yishan Zhou: Institute of Biochemistry and Molecular Biology, The Key Laboratory of Environment and Critical Human Diseases Prevention of the Education Department of Hunan Province, Hengyang Medical College, University of South China, Hengyang 421001, China
Haiyan Shen: Corresponding author.; Institute of Biochemistry and Molecular Biology, The Key Laboratory of Environment and Critical Human Diseases Prevention of the Education Department of Hunan Province, Hengyang Medical College, University of South China, Hengyang 421001, China

Journal volume & issue: Vol. 9, no. 12
p. e23079

Abstract

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Objective: To explore the mechanism of ursolic acid (UA) against acute B lymphoblastic leukaemia (B-ALL) based on network pharmacological analysis, molecular docking and experimental verification. Methods: The core targets, functional processes, and biological pathways of UA in B-ALL were predicted by network pharmacology and molecular docking. The efficacy and mechanism of UA against B-ALL were verified through in vitro experiments such as cell viability assays, CCK-8 assays, LDH assays, AO/EB staining, flow cytometry, and Western blot assays. Results: Network pharmacology analysis of the core targets indicated that the effects of UA on B-ALL were related to programmed cell death (apoptosis and pyroptosis). Molecular docking results showed that FOS, CASP8, MAPK8, IL-1β and JUN were the key targets of UA against B-ALL. The MTS assay showed that UA decreased the viability of Reh cells in a concentration- and time-dependent manner. Cellular and Western blot experiments found that UA induced Reh cell apoptosis and pyroptosis by upregulating the JNK signalling pathway. Conclusions: Our findings demonstrated that UA could induce Reh cell apoptosis and pyroptosis by activating the JNK signalling pathway to exert anti-B-ALL effects. This indicates that UA may become a potential drug for the effective treatment of B-ALL.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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