{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:12:21Z","timestamp":1792728741284,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2017A030312009, 2019A1515110613"],"award-info":[{"award-number":["2017A030312009, 2019A1515110613"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Gallic acid is an active phenolic acid widely distributed in plants, and there is compelling evidence to prove its anti-inflammatory effects. NLRP3 inflammasome dysregulation is closely linked to many inflammatory diseases. However, how gallic acid affects the NLRP3 inflammasome remains unclear. Therefore, in the present study, we investigated the mechanisms underlying the effects of gallic acid on the NLRP3 inflammasome and pyroptosis, as well as its effect on gouty arthritis in mice. The results showed that gallic acid inhibited lactate dehydrogenase (LDH) release and pyroptosis in lipopolysaccharide (LPS)-primed and ATP-, nigericin-, or monosodium urate (MSU) crystal-stimulated macrophages. Additionally, gallic acid blocked NLRP3 inflammasome activation and inhibited the subsequent activation of caspase-1 and secretion of IL-1\u03b2. Gallic acid exerted its inhibitory effect by blocking NLRP3-NEK7 interaction and ASC oligomerization, thereby limiting inflammasome assembly. Moreover, gallic acid promoted the expression of nuclear factor E2-related factor 2 (Nrf2) and reduced the production of mitochondrial ROS (mtROS). Importantly, the inhibitory effect of gallic acid could be reversed by treatment with the Nrf2 inhibitor ML385. NRF2 siRNA also abolished the inhibitory effect of gallic acid on IL-1\u03b2 secretion. The results further showed that gallic acid could mitigate MSU-induced joint swelling and inhibit IL-1\u03b2 and caspase 1 (p20) production in mice. Moreover, gallic acid could moderate MSU-induced macrophages and neutrophils migration into joint synovitis. In summary, we found that gallic acid suppresses ROS generation, thereby limiting NLRP3 inflammasome activation and pyroptosis dependent on Nrf2 signaling, suggesting that gallic acid possesses therapeutic potential for the treatment of gouty arthritis.<\/jats:p>","DOI":"10.3389\/fimmu.2020.580593","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:43:36Z","timestamp":1607301816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":262,"title":["Gallic Acid Alleviates Gouty Arthritis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Through Enhancing Nrf2 Signaling"],"prefix":"10.3389","volume":"11","author":[{"given":"Yuqing","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anli","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xican","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/nu11010023","article-title":"Inflammation and Oxidative Stress in an Obese State and the Protective Effects of Gallic Acid","volume":"11","author":"Dludla","year":"2018","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.10.056","article-title":"Alkyl esters of gallic acid as anticancer agents: A review","volume":"60","author":"Locatelli","year":"2013","journal-title":"Eur J Med Chem"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1039\/c5ra02727f","article-title":"Gallic acid: prospects and molecular mechanisms of its anticancer activity","volume":"5","author":"Subramanian","year":"2015","journal-title":"Rsc Adv"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2012.08.009","article-title":"Toona sinensis and its major bioactive compound gallic acid inhibit LPS-induced inflammation in nuclear factor-kappaB transgenic mice as evaluated by in vivo bioluminescence imaging","volume":"136","author":"Hsiang","year":"2013","journal-title":"Food Chem"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700699","article-title":"Gallic Acid and Gallates in Human Health and Disease: Do Mitochondria Hold the Key to Success","volume":"62","author":"Kosuru","year":"2018","journal-title":"Mol Nutr Food Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s12035-019-01759-7","article-title":"Gallic Acid Attenuated LPS-Induced Neuroinflammation: Protein Aggregation and Necroptosis","volume":"57","author":"Liu","year":"2020","journal-title":"Mol Neurobiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9364364","article-title":"Terminalia bellirica (Gaertn.) 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