{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:17:29Z","timestamp":1791001049959,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2628-B-197-001; MOST 108-2923-B-197-001-MY3; MOST 108-2811-B-197-500; MOST 108-2321-B-197-001"],"award-info":[{"award-number":["MOST 108-2628-B-197-001; MOST 108-2923-B-197-001-MY3; MOST 108-2811-B-197-500; MOST 108-2321-B-197-001"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education, Singapore","award":["MoE Tier 2 grant: R-143-000-478-112"],"award-info":[{"award-number":["MoE Tier 2 grant: R-143-000-478-112"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Gouty arthritis results from the generation of uric acid crystals within the joints. These uric acid crystals activate the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, which is involved in chronic inflammatory diseases, including gouty arthritis. This study identified the polyenylpyrrole derivative 4-hydroxy auxarconjugatin B (4-HAB), a novel autophagy inducer, which attenuated uric acid crystals-mediated activation of the NLRP3 inflammasome in vitro and in vivo. 4-HAB dose-dependently reduced the release of interleukin (IL)-1\u03b2, IL-18, active caspase-1 and apoptosis-associated speck-like protein (ASC) in uric acid crystals-activated macrophages. In a mechanistic study, 4-HAB was shown to inhibit uric acid crystals-induced mitochondrial damage, lysosomal rupture and ASC oligomerization. Additionally, 4-HAB inhibited the NLRP3 inflammasome through Sirt1-dependent autophagy induction. Furthermore, the anti-inflammatory properties of 4-HAB were confirmed in a mouse model of uric acid crystals-mediated peritonitis by the reduced levels of neutrophil influx, IL-1\u03b2, active caspase-1, IL-6 and MCP-1 in lavage fluids. In conclusion, 4-HAB attenuates gouty inflammation, in part by attenuating activation of the NLRP3 inflammasome through the Sirt1\/autophagy induction pathway.<\/jats:p>","DOI":"10.3390\/cells9020279","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T11:01:00Z","timestamp":1579863660000},"page":"279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-6779","authenticated-orcid":false,"given":"Chih-Yu","family":"Hsieh","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Animal Science, National Ilan University, Ilan 260, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan-Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei 10844, Taiwan"},{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11483, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0984-9492","authenticated-orcid":false,"given":"Yulin","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2952-6108","authenticated-orcid":false,"given":"Zhanxiong","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1625-5430","authenticated-orcid":false,"given":"Chin Heng","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerra Koteswara","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Animal Science, National Ilan University, Ilan 260, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Wen","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Animal Science, National Ilan University, Ilan 260, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ting","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Animal Science, National Ilan University, Ilan 260, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-4138","authenticated-orcid":false,"given":"Tz-Chuen","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Animal Science and Biotechnology, Tunghai University, Taichung 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-4863","authenticated-orcid":false,"given":"Fang-Hsin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3076-3637","authenticated-orcid":false,"given":"Oleg V.","family":"Chernikov","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry FEB RAS, Vladivostok 690022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May-Lan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science, Toko University, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Hua","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Department of Chinese Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei 10844, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Feng","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Animal Science, National Ilan University, Ilan 260, Taiwan"},{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11483, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12967-017-1141-8","article-title":"Immune modulation of some autoimmune diseases: The critical role of macrophages and neutrophils in the innate and adaptive immunity","volume":"15","author":"Navegantes","year":"2017","journal-title":"J. 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