{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:44:17Z","timestamp":1790300657326,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873612"],"award-info":[{"award-number":["81873612"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004609","name":"Foundation of Henan Educational Committee","doi-asserted-by":"publisher","award":["19B320019"],"award-info":[{"award-number":["19B320019"]}],"id":[{"id":"10.13039\/501100004609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004609","name":"Foundation of Henan Educational Committee","doi-asserted-by":"publisher","award":["20B320040"],"award-info":[{"award-number":["20B320040"]}],"id":[{"id":"10.13039\/501100004609","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Peritoneal fibrosis is a devastating complication in patients undergoing peritoneal dialysis, with no definite therapy yet available. <jats:italic>Salvia miltiorrhiza<\/jats:italic> and its major active component Salvianolic acid A (Sal A) have demonstrated a beneficial effect in myriad diseases. However, their effect on peritoneal fibrosis is unknown. In murine models of peritoneal dialysis, daily Sal A treatment substantially improved the peritoneal dialysis fluid (PDF) elicited peritoneal fibrosis, marked by thickening of the submesothelial compact zone, accumulation of extracellular matrix and increased expression of vimentin and PAI-1, concomitant with attenuation of GSK3\u03b2 hyperactivity. This coincided with diminished nitrotyrosine in peritoneal tissues and increased Nrf2 nuclear translocation, entailing a lessened oxidative injury and reinforced Nrf2 antioxidant response. Meanwhile, inflammatory infiltration and maladaptive angiogenesis in peritoneal tissues provoked by PDF injury were also mitigated by Sal A, associated with a suppressed NF\u03baB activation. Mechanistically, ectopic expression of the constitutively active GSK3\u03b2 blunted the NF\u03baB-suppressing and Nrf2-activating efficacy of Sal A in peritoneal mesothelial cells exposed to hypertonic dextrose, suggesting that GSK3\u03b2 inhibition mediates the protective effect of Sal A. Collectively, our findings may open the avenue for developing a novel therapy based on Sal A for preventing peritoneal fibrosis in peritoneal dialysis.<\/jats:p>","DOI":"10.3389\/fmed.2022.804899","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T06:40:55Z","timestamp":1646635255000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Therapeutic Targeting of GSK3\u03b2-Regulated Nrf2 and NF\u03baB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal 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