{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:47:58Z","timestamp":1774946878176,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Salidroside (2- (4-Hydroxyphenyl) ethyl \u03b2-D-glucopyranoside, SAL) is a bioactive compound present in Rhodiola rosea L., exhibiting diverse pharmacological properties such as anti-inflammatory and anti-fibrotic effects. Despite its known benefits, the therapeutic potential of SAL in peritoneal dialysis (PD) -induced peritoneal fibrosis remains unexplored. This study aims to investigate the protective effects of SAL in PD-related peritoneal fibrosis and its underlying mechanisms through the integration of single-cell RNA-seq, bulk RNA-seq, and network pharmacology analyses. A total of 249 disease targets were identified through single-cell RNA-seq and bulk RNA-seq analyses. Functional enrichment analysis highlighted the involvement of extracellular matrix organization, neutrophil degranulation, and the vitamin D receptor (VDR) pathway in peritoneal fibrosis. By intersecting 148 drug targets with the 249 disease targets, four therapeutic targets for SAL treatment against peritoneal fibrosis were pinpointed: cathepsin S, VDR, plasminogen activator urokinase, and galectin 3. In a murine model of peritoneal fibrosis induced by intraperitoneal injection of 4.25% PD fluid, SAL treatment significantly mitigated peritoneal fibrosis, as evidenced by reduced collagen deposition, decreased protein expression of \u03b1-smooth muscle actin and Collagen I, and a thinner peritoneum. <jats:italic>In vitro<\/jats:italic> experiments demonstrated that SAL treatment inhibited extracellular matrix deposition, potentially through upregulation of VDR expression. In conclusion, SAL may target VDR domains as a therapeutic agent for PD-related peritoneal fibrosis. These findings comprehensively identify potential therapeutic targets for SAL in combating peritoneal fibrosis, providing a theoretical basis for the clinical application of SAL in the treatment of peritoneal fibrosis.<\/jats:p>","DOI":"10.3389\/fphar.2025.1558366","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:22:13Z","timestamp":1750396933000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating single-cell RNA-seq, bulk RNA-seq and network pharmacology reveals protective effect of salidroside in peritoneal dialysis-associated peritoneal fibrosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Shuting","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qimei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenfen","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanjun","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianrui","family":"Dou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1186\/s12967-022-03623-0","article-title":"Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia","volume":"20","author":"Chen","year":"2022","journal-title":"J. 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