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ORIGINAL RESEARCH article

Front. Genet.
Sec. Computational Genomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1507606
This article is part of the Research Topic The role of genes and network pharmacology in new drug discovery View all articles

Systematic pharmacology-based strategy to investigate the mechanism of beta-sitosterol for treatment of rheumarthritis

Provisionally accepted
Xiaodong Wang Xiaodong Wang 1Jingxin Mao Jingxin Mao 1,2*
  • 1 Chongqing Medical and Pharmaceutical College, Chongqing, China
  • 2 Southwest University, Chongqing, China

The final, formatted version of the article will be published soon.

    Objective: β-sitosterol which derived from Vladimiriae Radix (VR) is used for the treatment of rheumatoid arthritis (RA), but the pharmacological mechanisms by that β-sitosterol affects RA have not been fully elucidated. Methods: Through TCMSP, PubChem, SwissTargetPrediction, Genecards, DisGeNET and OMIM databases, "β-sitosterol-RA" related genes were obtained respectively, and target protein interaction network (PPI) was constructed. GO and KEGG pathway enrichment analysis was carried out for the intersection genes. Use Discovery Studio 2019 software to perform molecular docking on MMP9, CASP3, HSP90AA1, SRC, EGFR and ALB genes respectively. βsitosterol was co-cultured with MH7A cells. The culture groups including control group (DMSO), positive drug group (methotrexate, 80 μmol/L), drug intervention group (10, 20, 40, 80, 160 μmol/L β-sitosterol) respectively. CCK8 method was used to investigate the inhibitory effect of β-sitosterol on the proliferation of MH7A cells. RT-PCR was used to analyze the mRNA expression of above core targets. Results: 41 genes between β-sitosterol and RA were obtained that mainly involving FoxO signaling pathway and PI3K Akt signaling pathway. The results of molecular docking suggested that β-sitosterol could bind to 6 core targets well. The experimental results showed that βsitosterol could significantly inhibit the excessive proliferation of MH7A cells (P<0.05). RT-PCR results showed that the expression of MMP9, HSP90AA1, SRC, EGFR and ALB core genes in the control group was significantly up-regulated while CASP3 gene was down regulated.Compared to control group, the mRNA expressions of MMP9, HSP90AA1, SRC, EGFR, ALB decreased (P<0.01) while the apoptosis related gene CASP3 increased in both of drug intervention group (80 μmol/L βsitosterol) and positive drug group (80 μmol/L methotrexate). Conclusion: Hence, β-sitosterol could contribute to the RA by modulating cell proliferation and regulating the aforementioned 6 core proteins, potentially through the regulation of the FoxO and PI3K-Akt signaling pathways.

    Keywords: rheumarthritis, Beta-sitosterol, experimental verification, Systematic pharmacology, Mechanism

    Received: 08 Oct 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Wang and Mao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jingxin Mao, Southwest University, Chongqing, China

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