{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:12:50Z","timestamp":1792789970474,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Province Science and Technology Department","award":["YDZJ202201ZYTS442"],"award-info":[{"award-number":["YDZJ202201ZYTS442"]}],"id":[{"id":"https:\/\/ror.org\/049x38272","id-type":"ROR","asserted-by":"crossref"}]},{"award":["YDZJ202201ZYTS442"],"award-info":[{"award-number":["YDZJ202201ZYTS442"]}],"id":[{"id":"https:\/\/ror.org\/049x38272","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Central Public-Interest Scientific Institution Basal Research Fund","award":["CAAS-ASTIP-ISAPS-2024"],"award-info":[{"award-number":["CAAS-ASTIP-ISAPS-2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Acute gouty arthritis (AGA) is an auto-inflammatory disorder characterized by dysregulated innate immune activation and overactive NOD-like receptor family pyrin domain-containing 3 (NLRP3)\/Toll-like receptor 4 (TLR4) inflammatory signaling. While adverse effects limit current therapies, the mechanism by which sunflower receptacle extract (SPE) alleviates gout remains unclear. Methods: This study investigated the anti-inflammatory mechanism of SPE in a male SPF-grade SD rat model of AGA induced by intra-articular monosodium urate crystals. Rats were orally administered SPE or colchicine, and ankle joint swelling, synovial histopathology, serum levels of tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1\u03b2(IL-1\u03b2), and interleukin-6 (IL-6), and synovial protein expression were assessed. Western blotting was used to assess the expression of the high-mobility group box 1 (HMGB-1), TLR4, and mitogen-activated protein kinase (MAPK) signaling pathways, as well as the activation of NLRP3. Results: Compared to the AGA group, treatment with colchicine and SPE significantly reduced ankle joint swelling, improved inflammatory infiltration in synovial tissue, and lowered serum levels of inflammatory factors TNF-\u03b1, IL-1\u03b2, and IL-6 (p &lt; 0.05, p &lt; 0.01). They also markedly decreased the expression of HMGB-1 and proteins in the TLR4, nuclear factor-\u0138B (NF-\u0138B), and MAPK pathways in joint synovial tissue (p &lt; 0.05, p &lt; 0.01, p &lt; 0.001). Conclusions: SPE markedly reduced joint swelling and synovial inflammatory infiltration, lowered serum TNF-\u03b1, IL-1\u03b2, and IL-6 levels, and decreased synovial expression of HMGB-1, TLR4, MyD88, TRAF6, and NF-\u0138B. Moreover, SPE suppressed NLRP3 inflammasome assembly and MAPK pathway activation. These results indicate that SPE mitigates AGA by inhibiting the HMGB-1-TLR4-NLRP3 inflammatory axis.<\/jats:p>","DOI":"10.3390\/nu18193290","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:34:31Z","timestamp":1791372871000},"page":"3290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sunflower Receptacle Extract Alleviates Acute Gouty Arthritis via HMGB1-TLR4-NLRP3 Inflammatory Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Zhiman","family":"Li","sequence":"first","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"},{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Huo","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Dong-E Ejiao Health Industry Technology Co., Ltd., Liaocheng 252201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1889-4984","authenticated-orcid":false,"given":"Yinshi","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.7150\/thno.95611","article-title":"Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis","volume":"14","author":"Yin","year":"2024","journal-title":"Theranostics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrrheum.2017.155","article-title":"Inflammation in gout:Mechanisms and therapeutic targets","volume":"13","author":"So","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/imr.12833","article-title":"Urate-induced immune programming: Consequences for gouty arthritis and hyperuricemia","volume":"294","author":"Popp","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, S., Zhang, L., Hao, D., Wang, L., Liu, J., Niu, Q., Mi, L., Peng, X., and Gao, J. (2022). Research progress of risk factors and early diagnostic biomarkers of gout-induced renal injury. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.908517"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41584-020-0441-1","article-title":"Global epidemiology of gout: Prevalence, incidence, treatment patterns and risk factors","volume":"16","author":"Dehlin","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.amjmed.2025.12.026","article-title":"Efficacy and safety of activated charcoal in primary gout: A double-blind, double-dummy, randomized controlled trial","volume":"139","author":"Guo","year":"2026","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0002-9343(84)90743-5","article-title":"Severe allopurinol toxicity.Description and guidelines for prevention in patients with renal insufficiency","volume":"76","author":"Hande","year":"1984","journal-title":"Am. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14474","DOI":"10.1021\/acs.jmedchem.3c01710","article-title":"Agents for the treatment of gout: Current advances and future perspectives","volume":"66","author":"Zeng","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"121467","DOI":"10.1016\/j.jep.2026.121467","article-title":"Anti-gout active ingredients from natural plant medicines and their related mechanisms","volume":"364","author":"Zhao","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119383","DOI":"10.1016\/j.indcrop.2024.119383","article-title":"Accumulated thermal units method for predicting development stages, and potential seed yield of sunflower (Helianthus annuus) under Mediterranean conditions","volume":"221","author":"Ippolitos","year":"2024","journal-title":"Ind. Crop Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4666","DOI":"10.1002\/fsn3.1783","article-title":"Oilseed crop sunflower (Helianthus annuus) as a source of food: Nutritional and health benefits","volume":"8","author":"Adeleke","year":"2020","journal-title":"Food Sci. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109094","DOI":"10.1016\/j.foodres.2020.109094","article-title":"Biotransformation of rice and sunflower side-streams by dikaryotic and monokaryotic strains of Pleurotus sapidus: Impact on phenolic profiles and bioactive properties","volume":"132","author":"Pinela","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_13","first-page":"852076","article-title":"Anti-Gouty arthritis and antihyperuricemia effects of sunflower (Helianthus annuus) head extract in gouty and hyperuricemia animal models","volume":"017","author":"Li","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104055","DOI":"10.1016\/j.jff.2020.104055","article-title":"Sunflower head enzymatic hydrolysate relives hyperuricemia by inhibiting crucial proteins (xanthine oxidase, adenosine deaminase, uric acid transporter1) and restoring gut microbiota in mice","volume":"72","author":"Liu","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dai, H., Lv, S., Qiao, Z., Wang, K., Zhou, X., and Bao, C. (2022). The active components of sunflower (Helianthus annuus L.) calathide and the effects on urate nephropathy based on COX-2\/PGE2 signaling pathway and the urate transporter URAT1, ABCG2 and GLUT9. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.769555"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110466","DOI":"10.1016\/j.intimp.2023.110466","article-title":"Immune and inflammatory mechanisms and therapeutic targets of gout: An update","volume":"121","author":"Liu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/art.43215","article-title":"Gout and NLRP3 Inflammasome Biology","volume":"77","author":"Poulsen","year":"2025","journal-title":"Arthritis Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, Z., Yu, Y., Sun, Q., Li, Z., Huo, X., Sha, J., Qu, D., and Sun, Y. (2025). Based on the TLR4\/NLRP3 pathway and its impact on the formation of NETs to explore the mechanism of ginsenoside Rg1 on acute gouty arthritis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094233"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119231","DOI":"10.1016\/j.jep.2024.119231","article-title":"Palmatine, an isoquinoline alkaloid from Phellodendron amurense Rupr., ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome","volume":"340","author":"Jiang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103255","DOI":"10.1016\/j.redox.2024.103255","article-title":"Inhibition of ferroptosis rescues M2 macrophages and alleviates arthritis by suppressing the HMGB1\/TLR4\/STAT3 axis in M1 macrophages","volume":"75","author":"Feng","year":"2024","journal-title":"Redox Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Andersson, U., Tracey, K.J., and Yang, H. (2021). Post-translational modification of HMGB1 disulfide bonds in stimulating and inhibiting inflammation. Cells, 10.","DOI":"10.3390\/cells10123323"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.apsb.2022.12.001","article-title":"A novel IRAK4\/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR\/MYD88-mediated NF-\u0138B pathway","volume":"13","author":"Yoon","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112767","DOI":"10.1016\/j.intimp.2024.112767","article-title":"Geraniin from the methanol extract of Pilea mongolica suppresses LPS-induced inflammatory responses by inhibiting IRAK4\/MAPKs\/NF-\u0138B\/AP-1 pathway in HaCaT cells","volume":"140","author":"An","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111690","DOI":"10.1016\/j.brainresbull.2025.111690","article-title":"Alpha-Bisabolol alleviates LPS-reduced hippocampal neurogenesis and cognitive function by anti-inflammatory action via downregulating MAPK and NF-\u0138B signaling in mice","volume":"234","author":"Kim","year":"2026","journal-title":"Brain Res. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118372","DOI":"10.1016\/j.biopha.2025.118372","article-title":"Methanol extract of Euphorbia cotinifolia L. leaf attenuates inflammation and oxidative stress in RAW 264.7 macrophages via TAK1-mediated suppression of NF-\u0138B\/MAPK and activation of Nrf2 pathways","volume":"190","author":"Lee","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"157848","DOI":"10.1016\/j.phymed.2026.157848","article-title":"Phaseoloidin, a homogentisic acid glucoside from Entada phaseoloides, suppresses gout inflammation via NLRP3 inflammasome","volume":"152","author":"Jiang","year":"2026","journal-title":"Phytomedicine"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T04:12:28Z","timestamp":1791691948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":26,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["nu18193290"],"URL":"https:\/\/doi.org\/10.3390\/nu18193290","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}