{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:02:57Z","timestamp":1777006977634,"version":"3.51.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE030495"],"award-info":[{"award-number":["R01DE030495"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE027404"],"award-info":[{"award-number":["R01DE027404"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"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>Gout is an acute inflammatory arthritis triggered by monosodium urate (MSU) crystal deposition and activation of innate immune responses. In addition to inflammasome signaling, emerging evidence suggests that metabolic reprogramming of arachidonic acid (AA) pathways amplifies inflammatory responses during gout flares. However, the contribution of upstream fatty acid desaturation processes that regulate endogenous AA availability remains poorly defined. 1,2,3,4,6-Penta-O-galloyl-\u03b2-D-glucose (PGG) is a naturally occurring polyphenol with reported anti-inflammatory activity, but its effects on MSU-induced fatty acid metabolism and gouty inflammation have not been well established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Publicly available bulk and single-cell transcriptomic datasets from human and mouse gout studies were analyzed to assess dysregulation of AA-associated pathways. MSU-induced inflammatory responses were examined in mouse bone marrow\u2013derived macrophages and in a murine MSU-induced gout model. Macrophages were treated with PGG prior to MSU stimulation, and inflammatory cytokine production, phagocytosis, and expression of fatty acid desaturases were assessed. Lipidomic analysis of macrophages and plasma was performed using gas chromatography\u2013mass spectrometry (GC\u2013MS) to quantify arachidonic acid and related fatty acids.\n                      <jats:italic>In vivo<\/jats:italic>\n                      disease severity, cytokine expression, and anti-inflammatory markers were evaluated following PGG treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of public datasets revealed consistent dysregulation of arachidonic acid\u2013associated inflammatory pathways during gout flares. In macrophages, MSU stimulation increased expression of fatty acid desaturases FADS1 and FADS2 and promoted accumulation of arachidonic acid, concomitant with robust production of pro-inflammatory cytokines. PGG treatment significantly suppressed MSU-induced FADS1, FADS2 and arachidonic acid levels, and attenuated pro-inflammatory cytokine production. PGG also markedly impaired macrophage phagocytosis of MSU crystals.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , PGG treatment significantly reduced clinical disease severity in an MSU-induced gout model, suppressed fatty acid desaturation and arachidonic acid accumulation in plasma, decreased pro-inflammatory cytokine expression, and enhanced anti-inflammatory markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify fatty acid desaturation as an important metabolic contributor to gouty inflammation and demonstrate that PGG suppresses MSU-induced inflammation by limiting endogenous arachidonic acid availability, reducing inflammatory amplification, and impairing MSU crystal phagocytosis. Targeting upstream fatty acid metabolism represents a potential therapeutic strategy for modulating acute gout flares beyond conventional anti-inflammatory approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1812913","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:31:48Z","timestamp":1777005108000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pentagalloyl glucose suppresses MSU crystal\u2013induced gout inflammation and arachidonic acid production in vitro and in vivo"],"prefix":"10.3389","volume":"17","author":[{"given":"Sadiq","family":"Umar","sequence":"first","affiliation":[{"name":"Department of Oral Biology, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sugasini","family":"Dhavamani","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetes and Metabolism, Department of medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poorna C. 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