{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:48:36Z","timestamp":1785923316191,"version":"3.56.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatic steatosis, inflammation, and fibrosis, yet effective pharmacological therapies remain limited. Melandrii Herba, a traditional East Asian medicinal herb used to improve blood circulation and relieve inflammatory disorders, has reported anti-inflammatory activity. However, its therapeutic potential and active constituents in MASH remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study investigated the hepatoprotective and anti-fibrotic effects of Melandrii Herba ethanol extract (MHE) and its purified constituent melandryoside in MASH and explored the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Palmitic acid-challenged HepG2 hepatocytes and TGF-\u03b2-stimulated HSC-LX2 cells were used to evaluate metabolic and fibrogenic stress responses.\n                      <jats:italic>In vivo<\/jats:italic>\n                      efficacy was examined in choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice, with MHE administered therapeutically after disease establishment (weeks 8\u201312) under continued dietary challenge. Interactome analysis, co-immunoprecipitation, and PPM1A loss-of-function approaches were used to investigate the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MHE reduced lipid accumulation and oxidative stress in palmitic acid-treated hepatocytes and suppressed TGF-\u03b2-induced hepatic stellate cell activation, fibrogenic gene expression, and SMAD2\/3 phosphorylation in HSC-LX2 cells. In CDAHFD-fed mice, oral administration of MHE attenuated hepatic steatosis, inflammatory injury, and collagen deposition. Mechanistically, MHE and melandryoside restored PPM1A-SMAD interaction and reduced SMAD2\/3 phosphorylation, whereas PPM1A knockdown diminished their anti-fibrotic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MHE and melandryoside alleviated pathological features of MASH by reducing metabolic stress and suppressing fibrotic signaling. These findings identify melandryoside as a bioactive constituent of Melandrii Herba and suggest that regulation of PPM1A-SMAD signaling may represent a potential therapeutic strategy for MASH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1880176","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:37:56Z","timestamp":1785922676000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Melandryoside attenuates steatohepatitis and fibrosis by restoring PPM1A-mediated SMAD signaling termination"],"prefix":"10.3389","volume":"17","author":[{"given":"Yo Han","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)","place":["Ulsan, Republic of 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