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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1515038

Integrated Serum Metabolomics and Network Pharmacology reveal molecular mechanism of Qixue Huazheng Formula on Peritoneal Fibrosis

Provisionally accepted
Xiaohui Meng Xiaohui Meng 1Li Sheng Li Sheng 1Yongqing You Yongqing You 1Huibo Dai Huibo Dai 1Manshu Yu Manshu Yu 2Funing Wang Funing Wang 1Ziren Zhou Ziren Zhou 1Yun Shan Yun Shan 2*Meixiao Sheng Meixiao Sheng 2*
  • 1 Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
  • 2 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

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

    Background: Peritoneal fibrosis (PF) causes peritoneal dialysis (PD) withdrawal due to ultrafiltration failure. Qixue Huazheng formula (QXHZF), comprising Astragalus membranaceus, Centella asiatica, and Ligusticum sinense, is applied to treat PD-related peritoneum injury related; however, the active components, core genes, and underlying mechanism involved remain unclear.The anti-PF effects of QXHZF were verified in vivo and in vitro. Targets underlying QXHZF-mediated improvement of PD-induced PF were predicted using network pharmacology analysis. Metabolites associated with QXHZF treatment of PD-related PF were analyzed by serum metabolomics. Integration of network pharmacology and serum metabolomics findings identified potentially important pathways, metabolites, and targets, and molecular docking studies confirmed the interactions of key components and targets. Western blotting (WB), quantitative real-time PCR (qRT-PCR), TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and flow cytometry were conducted.Results: QXHZF had potent therapeutic efficacy against PF according to WB, qRT-PCR, and pathological section examination. Network pharmacological analysis indicated that multiple QXHZF compounds contributed to improving PF by modulating various targets and pathways. Differential metabolites were identified by serum metabolomics analysis. Integrated data analysis indicated that steroid hormone biosynthesis, the Ras signaling pathway, apoptosis, and estrogen signaling contributed to the effects of QXHZF. Metabolite-target network and molecular docking analyses revealed that QXHZF can bind to estrogen receptor 1 (ESR1) and rapidly accelerated fibrosarcoma 1 (RAF1) through its components. WB demonstrated that QXHZF treatment reversed activation of the above-mentioned signaling pathways, thereby inhibiting PD fluid-induced PF.QXHZF can significantly ameliorate PD-induced PF and may regulate estrogen signaling, the Ras pathway, and apoptosis in this context.

    Keywords: Traditional Chinese Medicine, Qixue Huazheng formula, Peritoneal Fibrosis, Metabolomics, Network Pharmacology, estrogen signaling, Ras pathway, Apoptosis

    Received: 22 Oct 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Meng, Sheng, You, Dai, Yu, Wang, Zhou, Shan and Sheng. 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:
    Yun Shan, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
    Meixiao Sheng, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

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