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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1447283

Multi-omics analysis to reveal the synergistic mechanism underlying the multiple ingredients of Stephania tetrandra extract on rheumatoid arthritis through the PI3K/Akt signaling pathway

Provisionally accepted
Jinfeng Chen Jinfeng Chen *An Zhang An Zhang Anzheng Nie Anzheng Nie Xiaoxiao Zuo Xiaoxiao Zuo Lei Zhang Lei Zhang Yuxue Jiao Yuxue Jiao Lulu Wang Lulu Wang Yang Yang Yang Yang Kun Liu Kun Liu Xinli Xue Xinli Xue Yuanyuan Zhuang Yuanyuan Zhuang Yansha Meng Yansha Meng Jing-Hua Yang Jing-Hua Yang *
  • First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

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

    Stephania tetrandra has been used for treating rheumatic diseases for thousands of years in rural areas of China. Several studies have found that tetrandrine and fangchinoline can inactivate the PI3K/Akt signaling pathway by reducing the expression and phosphorylation of AKT. However, the mechanism underlying the therapeutic actions of S. tetrandra on RA is not well known. In this study, we determined the molecular mechanism of the therapeutic effects of the multiple ingredients of S. tetrandra extract (STE) on collagen-induced arthritic (CIA) rats by integrating pharmacometabolomics, proteomics, and PTMomics. In the multi-omics joint analysis, first, the expression signatures of proteins, PTMs, metabolites, and STE ingredients were profiled in CIA rats' PBMCs that underwent STE treatment. Bioinformatics analysis were subsequently probed that STE mainly regulated tryptophan metabolism, inflammatory response, and cell adhesion pathways in CIA rats. The interrelated pathways were further constructed, and the findings revealed that STE attenuated the inflammatory response and proliferation of PBMCs in CIA rats by mediating the key targets of the PI3K/Akt pathway, including Hint1, ACP1, FGR, HSP90@157W+dioxidation, and Prkca@220N+845.4540 Da. The rheumatic functions of Hint1 and ACP1 were further confirmed by applying a transcriptomic data of RA patients who clinically received abatacept therapy. Furthermore, a cross-ome correlation analysis was performed and major in vivo ingredients of STE, including coclaurine-N-glucuronide, Me,coclaurine-O-glc, N-gluA-schefferine, corydamine, corypamine, tetrandrine, and fangchiniline, were found to act on these targerts to inactivate the PI3K/Akt pathway. These results elucidated the molecular mechanism by which the ingredients of STE mediate the expression of the key targets in the PI3K/Akt pathway, leading to anti-rheumatic functions. The findings of this study provided new insights into the synergistic effect of STE against arthritis in rats.

    Keywords: Stephania tetrandra, multi-omics joint analysis, Rheumatoid arthritis, PI3K/Akt pathway, Synergistic mechanism, abatacept therapy

    Received: 11 Jun 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Chen, Zhang, Nie, Zuo, Zhang, Jiao, Wang, Yang, Liu, Xue, Zhuang, Meng and Yang. 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:
    Jinfeng Chen, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
    Jing-Hua Yang, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

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