{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:29:04Z","timestamp":1782210544135,"version":"3.54.5"},"reference-count":35,"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:sec><jats:title>Background:<\/jats:title><jats:p>The role of nucleotide-binding oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome and pyroptosis in the inflammatory microenvironment of metabolic-associated fatty liver disease (MASLD) has been posited as crucial. <jats:italic>Bletilla striata<\/jats:italic> polysaccharides (BSPs), extracted from the tubers of <jats:italic>Bletilla striata (Thunb.) Rchb.f.<\/jats:italic>, exhibit significant anti-inflammatory properties. However, their potential protective effects on MASLD and their role in regulating pyroptosis remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives:<\/jats:title><jats:p>This study investigates the efficacy of BSP-1, a purified metabolite isolated from crude BSPs, on MASLD by evaluating its ability to modulate the NLRP3\/caspase-1\/GSDMD signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>To simulate MASLD <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, high-fat diet (HFD)-induced rat models and free fatty acid (FFA)-stimulated HepG2 cells were used. Serum indicators and histopathological staining were employed to assess liver injury and lipid deposition. Additionally, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), immunofluorescence, real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB) analysis were conducted to examine the NLRP3\/caspase-1\/GSDMD pathway and related cytokine levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>BSP-1 significantly ameliorates alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels in both rat serum and HepG2 cells. Furthermore, BSP-1 reduces inflammatory factors interleukin (IL)-1\u03b2 and IL-18, while improving pathological changes in rat liver tissue. Mechanistically, BSP-1 regulates the expression of pyroptosis-related proteins and mRNAs in the NLRP3\/caspase-1\/GSDMD pathway, thereby protecting against MASLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion:<\/jats:title><jats:p>BSP-1 may represent a promising therapeutic agent for MASLD treatment by inhibiting the NLRP3\/caspase-1\/GSDMD signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1563275","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:51:59Z","timestamp":1750409519000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Tingting","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1146\/annurev-pathmechdis-032521-102529","article-title":"Role of the inflammasome in liver disease","volume":"17","author":"Carvalho Ribeiro","year":"2022","journal-title":"Annu. 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