Abstract
Peritoneal dialysis (PD) is the mainstay of treatment for renal failure replacement therapy. Although PD has greatly improved the quality of life of end-stage renal disease (ESRD) patients, long-term PD can lead to ultrafiltration failure, which in turn causes peritoneal fibrosis (PF). Silymarin (SM) is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) species that has a variety of pharmacological actions, including antioxidant, anti-inflammatory, antiviral, and anti-fibrotic pharmacological activities. However, the effect of SM on PF and its potential mechanisms have not been clarified. The aim of this study was to investigate the preventive effect of SM on PF in vitro and in vivo as well as elucidate the underlying mechanisms. We established PF mouse models and human pleural mesothelial cell fibrosis in vitro by intraperitoneal injection of high-glucose peritoneal dialysis solution (PDS) or transforming growth factor-β1 (TGF-β1), and evaluated the effect of SM on peritoneal fibrosis in vivo and in vitro. We found that SM alleviated peritoneal dysfunction. Meanwhile, SM inhibited the expression of fibrotic markers (TGF-β1, collagen I, fibronectin) and restored the expression of E-cadherin, BMP-7 in PF mice and TGF-β1-treated Met-5A cells. Furthermore, SM markedly down-regulated the expression of TGF-β1, p-Smad2, and p-Smad3 and up-regulated the expression of smad7. In conclusion, these findings suggested that SM may be an efficient and novel therapy for the prevention of PF through inhibition of TGF-β/Smad signaling.
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Data availability
The datasets generated during and/or analyzed during the current study are not publicly available due to reasons way date are not public, but are available from the corresponding author on reasonable request.
The study protocol and animal handling procedures were approved by the Experimental Animal Ethics Committee of Nanjing Hospital Affiliated to Nanjing Medical University (Ethical approval number: DWSY-22045176).
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Funding
This work was supported by the National Natural Science Foundation of China (No.81903684); the Hospital Pharmacy Research Foundation of Changzhou Siyao Hospital and Nanjing Pharmaceutical Association (2019YX019); the Fundamental Research Funds for the Central Universities (021414380498); Foundation of Nanjing Medical Center for Clinical Pharmacy.
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Yingwen Bai conducted the experiments and wrote the manuscript. Lulu Wang conceived and designed the study and helped conduct it. TingYang and Lingyun Wang conducted statistical analysis and data analysis. Weihong Ge edited and revised the manuscript, revised and approved the final manuscript. All authors contributed to manuscript revision, read, and approved the submitted version. The authors confirm that all data were generated in-house and that no paper mill was used.
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Bai, Y., Wang, L., TingYang et al. Silymarin ameliorates peritoneal fibrosis by inhibiting the TGF-β/Smad signaling pathway. Naunyn-Schmiedeberg's Arch Pharmacol 396, 2379–2391 (2023). https://doi.org/10.1007/s00210-023-02450-4
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DOI: https://doi.org/10.1007/s00210-023-02450-4