{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:49:42Z","timestamp":1791967782273,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008758","name":"Council of Science and Technology, U.P.","doi-asserted-by":"publisher","award":["CST\/D\u2010796"],"award-info":[{"award-number":["CST\/D\u2010796"]}],"id":[{"id":"10.13039\/501100008758","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic kidney disease (CKD) is driven by persistent inflammation and progressive fibrosis, leading to irreversible renal damage. Gramine (GMN), an indole alkaloid, has broad pharmacological benefits. However, its therapeutic potential against renal fibrosis remains unexplored. This study investigates the antifibrotic potential of GMN in an experimental model of CKD. Potential therapeutic targets of GMN associated with renal fibrosis were identified through network analysis, and functional enrichment analysis revealed the mechanisms regulated by these targets. In\u00a0vitro validation was conducted in transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21)\u2010induced normal rat kidney fibroblast (NRK\u201049F) cells. Fibrosis in the left kidney was induced by ureter obstruction, and mice received GMN orally at doses of 10 and 30\u2009mg\/kg. GMN targets 110 genes related to renal fibrosis that regulate profibrotic pathways, including TGF\u2010\u03b21\u2010mediated canonical Smad signaling. GMN effectively attenuated TGF\u2010\u03b21\u2010induced fibroblast\u2010to\u2010myofibroblast transition by inhibiting Smad signaling, resulting in downregulation of collagen I and fibronectin. In\u00a0vivo, oral administration of GMN ameliorated the histopathological damage induced by UUO and significantly improved renal function. Mechanistically, GMN suppressed NF\u2010\u03baB\u2010mediated priming of the NOD\u2010like receptor pyrin domain\u2010containing 3 (NLRP3) inflammasome and inhibited IL\u20101\u03b2 maturation, thereby mitigating renal inflammation. UUO\u2010induced fibrotic responses, characterized by upregulation of TGF\u2010\u03b21, TGF\u2010\u03b2 receptor type II, p\u2010Smad2\/3, connective tissue growth factor (CTGF), alpha\u2010smooth muscle actin, and extracellular matrix (ECM) components were significantly attenuated by GMN, suggesting its ability to inhibit pathological ECM remodeling. This study demonstrates that GMN attenuates renal inflammation, suppresses myofibroblast activation and ECM remodeling by concurrently inhibiting NF\u2010\u03baB\/NLRP3 inflammasome axis and TGF\u2010\u03b21\/Smad pathway.<\/jats:p>","DOI":"10.1002\/ptr.70470","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:14:18Z","timestamp":1791965658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gramine Suppresses Myofibroblast Activation and ECM Accumulation in Renal Fibrosis by Targeting the NF\u2010\u03baB\/NLRP3 and TGF\u2010\u03b21\/Smad Pathways"],"prefix":"10.1002","author":[{"given":"Shobhit","family":"Gairola","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and Research, Raebareli (NIPER\u2010R)  Lucknow Uttar Pradesh 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