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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1418485

Astragalus membranaceus and its monomers treat peritoneal fibrosis and related muscle atrophy through the AR/TGF-β1 pathway

Provisionally accepted
Li Sheng Li Sheng 1Jinyi Sun Jinyi Sun 1Liyan Huang Liyan Huang 1Manshu Yu Manshu Yu 1Xiaohui Meng Xiaohui Meng 1Yun Shan Yun Shan 1Xuemei Sun Xuemei Sun 1Funing Wang Funing Wang 1Jun Shi Jun Shi 2Meixiao Sheng Meixiao Sheng 1*
  • 1 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
  • 2 Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China

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

    Backgroud: To anticipate the potential molecular mechanism of Astragalus membranaceus (AM) and its monomer, Calycosin, against peritoneal fibrosis (PF) and related muscle atrophy using mRNA-seq, network pharmacology, and serum pharmacochemistry.Methods: Animal tissues were examined to evaluate a CKD-PF mice model construction. mRNA sequencing was performed to find differential targets. The core target genes of AM against PF were screened through network pharmacology analysis, and CKD-PF mice models were given high-and low-dose AM to verify common genes. Serum pharmacochemistry was conducted to clarify which components of AM can enter the blood circulation, and the selected monomer was further validated through cell experiments for the effect on PF and mesothelial mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs).Results: The CKD-PF mice models were successfully constructed. A total of 31,184 genes were detected in the blank and CKD-PF groups, and 228 transcription factors had significant differences between the groups. Combined with network pharmacology analysis, a total of 228 AM-PF-related targets were identified. Androgen receptor (AR) was the remarkable transcription factor involved in regulating transforming growth factor-β1 (TGF-β1). AM may be involved in regulating the AR/TGF-β1 signaling pathway and may alleviate peritoneal dialysis-related fibrosis and muscle atrophy in CKD-PF mice. In 3% peritoneal dialysis solution-stimulated HMrSV5 cells, AR expression levels were dramatically reduced, whereas TGF-β1/p-smads expression levels were considerably increased.Conclusions: AM could ameliorate PF and related muscle atrophy via the co-target AR and modulated AR/TGF-β1 pathway. Calycosin, a monomer of AM, could partially reverse PMC MMT via the AR/TGF-β1/smads pathway. This study explored the traditional Chinese medicine theory of "same treatment for different diseases," and supplied the pharmacological evidence of "AM can treat flaccidity syndrome.

    Keywords: Astragalus membranaceus, Calycosin, Peritoneal Fibrosis, Mesothelial mesenchymal transition, muscle atrophy, AR/TGF-β1 signaling pathway, mRNA sequencing, Network Pharmacology

    Received: 16 Apr 2024; Accepted: 16 Jul 2024.

    Copyright: © 2024 Sheng, Sun, Huang, Yu, Meng, Shan, Sun, Wang, Shi 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: Meixiao Sheng, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

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