{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:49:22Z","timestamp":1782452962249,"version":"3.54.5"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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>Gentisic acid (GA), a natural polyphenolic compound, possesses significant anti-inflammatory activity, but its molecular mechanism, particularly its association with the intestinal microbiota and specific signaling pathways, remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      In this study, we aimed to clarify anti-inflammatory targets, pathways and mechanism of GA using network pharmacology,\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments, and microbiome analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Network pharmacology was used to predict the anti-inflammatory targets and pathways of GA. Lipopolysaccharide (LPS)-induced RAW 264.7 cell models and oxazolone (OXA)-induced zebrafish models were established to evaluate the anti-inflammatory effects of GA. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and 16S rDNA sequencing were used to detect changes in key genes, proteins, and intestinal microbiota, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      GA significantly attenuated LPS- and OXA-induced inflammation, reducing nitric oxide (NO) levels and inflammatory cytokines (IL-1\u03b2, TNF-\u03b1, and IL-6) in RAW 264.7 cells, along with IL-6 and IL-1\u03b2 levels in zebrafish intestinal tissues. It was associated with the regulation of the IL-17 signaling pathway, reducing the abundance of\n                      <jats:italic>Acinetobacter<\/jats:italic>\n                      ,\n                      <jats:italic>Allorhizobium\u2013Neorhizobium\u2013Pararhizobium\u2013Rhizobium<\/jats:italic>\n                      , and\n                      <jats:italic>Shewanella<\/jats:italic>\n                      , which were positively correlated with key genes (IKK\u03b1, IKK\u03b2, TRAF6, etc.) in the IL-17 pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GA may exert anti-inflammatory effects potentially via correlatively regulating the composition of pathogenic intestinal bacteria to maintain microecological homeostasis and modulating the IL-17\/NF-\u03baB pathway. These correlative findings provide a valuable reference for the research and development of polyphenolic compounds.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1837686","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:44:08Z","timestamp":1782452648000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on the anti-inflammatory effects and mechanisms of gentisic acid based on the LPS-induced RAW264.7 cell inflammation model and the oxazolone-induced zebrafish inflammation model"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Han","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Pekin Union Medical College Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Feed Research of Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zufeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Feed Research of Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Feed Research of Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Feed Research of Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Feed Research of Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Pekin Union Medical College Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Feed Research of Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1002\/ptr.6573","article-title":"A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: comprehensive pharmacology, toxicology, and some pharmaceutical aspects","volume":"34","author":"Abedi","year":"2020","journal-title":"Phytother. 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