{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:25:41Z","timestamp":1772609141296,"version":"3.50.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960663"],"award-info":[{"award-number":["81960663"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008111","name":"Hainan Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["SZR190055"],"award-info":[{"award-number":["SZR190055"]}],"id":[{"id":"10.13039\/501100008111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Med Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of<jats:italic>Stephania hainanensis<\/jats:italic>(<jats:italic>S. hainanensis<\/jats:italic>) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After oral administration of SHA (10 or 20\u2009mg\/kg) or the antigout medicine colchicine (0.5\u2009mg\/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5\u2009mg\/50\u2009\u03bcl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2\u2009days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48\u2009h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1\u03b2 and TNF-\u03b1. In addition, NLRP3, Caspase-1 and IL-1\u03b2, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12906-021-03364-5","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T13:03:23Z","timestamp":1626786203000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice"],"prefix":"10.1186","volume":"21","author":[{"given":"Hao-fei","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-yue","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao-lin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-qian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-chong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dao-rui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-liang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4965-0007","authenticated-orcid":false,"given":"Qi-bing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"issue":"5","key":"3364_CR1","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.jare.2017.04.008","volume":"8","author":"G Ragab","year":"2017","unstructured":"Ragab G, Elshahaly M, Bardin T. Gout: an old disease in new perspective - a review. J Adv Res. 2017;8(5):495\u2013511. https:\/\/doi.org\/10.1016\/j.jare.2017.04.008.","journal-title":"J Adv Res"},{"issue":"1","key":"3364_CR2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13075-015-0550-4","volume":"17","author":"C Pineda","year":"2015","unstructured":"Pineda C, Fuentes-Gomez AJ, Hernandez-Diaz C, Zamudio-Cuevas Y, Fernandez-Torres J, Lopez-Macay A, et al. Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout. Arthritis Res Ther. 2015;17(1):37. https:\/\/doi.org\/10.1186\/s13075-015-0550-4.","journal-title":"Arthritis Res Ther"},{"issue":"7","key":"3364_CR3","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/s41584-020-0441-1","volume":"16","author":"M Dehlin","year":"2020","unstructured":"Dehlin M, Jacobsson L, Roddy E. Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 2020;16(7):380\u201390. https:\/\/doi.org\/10.1038\/s41584-020-0441-1.","journal-title":"Nat Rev Rheumatol"},{"issue":"9","key":"3364_CR4","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.4049\/jimmunol.1801097","volume":"202","author":"Y Yu","year":"2019","unstructured":"Yu Y, Yang J, Fu S, Xue Y, Liang M, Xuan D, et al. Leptin promotes monosodium urate crystal-induced inflammation in human and murine models of gout. J Immunol. 2019;202(9):2728\u201336. https:\/\/doi.org\/10.4049\/jimmunol.1801097.","journal-title":"J Immunol"},{"issue":"1","key":"3364_CR5","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s13075-018-1550-y","volume":"20","author":"Q Yang","year":"2018","unstructured":"Yang Q, Zhang Q, Qing Y, Zhou L, Mi Q, Zhou J. miR-155 is dispensable in monosodium urate-induced gouty inflammation in mice. Arthritis Res Ther. 2018;20(1):144.","journal-title":"Arthritis Res Ther"},{"key":"3364_CR6","doi-asserted-by":"publisher","first-page":"795","DOI":"10.2147\/PPA.S97927","volume":"11","author":"T Aung","year":"2017","unstructured":"Aung T, Myung G, FitzGerald JD. Treatment approaches and adherence to urate-lowering therapy for patients with gout. Patient Prefer Adherence. 2017;11:795\u2013800. https:\/\/doi.org\/10.2147\/PPA.S97927.","journal-title":"Patient Prefer Adherence"},{"issue":"4","key":"3364_CR7","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1080\/14740338.2017.1284199","volume":"16","author":"N Schlesinger","year":"2017","unstructured":"Schlesinger N. The safety of treatment options available for gout. Expert Opin Drug Saf. 2017;16(4):429\u201336. https:\/\/doi.org\/10.1080\/14740338.2017.1284199.","journal-title":"Expert Opin Drug Saf"},{"issue":"1","key":"3364_CR8","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s12916-017-0890-9","volume":"15","author":"T Bardin","year":"2017","unstructured":"Bardin T, Richette P. Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options. BMC Med. 2017;15(1):123. https:\/\/doi.org\/10.1186\/s12916-017-0890-9.","journal-title":"BMC Med"},{"issue":"4","key":"3364_CR9","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/cbdd.13437","volume":"93","author":"A Mehmood","year":"2019","unstructured":"Mehmood A, Ishaq M, Zhao L, Safdar B, Rehman AU, Munir M, et al. Natural compounds with xanthine oxidase inhibitory activity: a review. Chem Biol Drug Des. 2019;93(4):387\u2013418. https:\/\/doi.org\/10.1111\/cbdd.13437.","journal-title":"Chem Biol Drug Des"},{"key":"3364_CR10","doi-asserted-by":"crossref","first-page":"3095624","DOI":"10.1155\/2020\/3095624","volume":"2020","author":"R Yao","year":"2020","unstructured":"Yao R, Geng Z, Mao X, Bao Y, Guo S, Bao L, et al. Tu-Teng-Cao extract alleviates monosodium urate-induced acute gouty arthritis in rats by inhibiting uric acid and inflammation. Evid Based Complement Alternat Med. 2020;2020:3095624.","journal-title":"Evid Based Complement Alternat Med"},{"key":"3364_CR11","volume-title":"Flora of China","author":"China ECoFo","year":"1996","unstructured":"China ECoFo. Flora of China. Beijing: Science Press; 1996."},{"key":"3364_CR12","volume-title":"Pharmacopoeia of the People\u2019s republic of China","author":"Commission CP","year":"2015","unstructured":"Commission CP. Pharmacopoeia of the People\u2019s republic of China. Beijing: China medical science press; 2015."},{"issue":"3\u20134","key":"3364_CR13","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/pca.2618","volume":"27","author":"J He","year":"2016","unstructured":"He J, Liu Y, Kang Y, Yang P, Wang Y, Guo J, et al. Identification of alkaloids in Stephania hainanensis by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Phytochem Anal. 2016;27(3\u20134):206\u201316. https:\/\/doi.org\/10.1002\/pca.2618.","journal-title":"Phytochem Anal"},{"issue":"2","key":"3364_CR14","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jep.2010.08.047","volume":"132","author":"DK Semwal","year":"2010","unstructured":"Semwal DK, Badoni R, Semwal R, Kothiyal SK, Singh GJ, Rawat U. The genus Stephania (Menispermaceae): chemical and pharmacological perspectives. J Ethnopharmacol. 2010;132(2):369\u201383. https:\/\/doi.org\/10.1016\/j.jep.2010.08.047.","journal-title":"J Ethnopharmacol"},{"issue":"6","key":"3364_CR15","first-page":"719","volume":"11","author":"C M.","year":"2011","unstructured":"M. C, Zhu Y, Dong Z, Zhao Y, Yang J. Analgesic and anti-inflammatory effects of total alkaloids from Stephania hainanensis in Hainan and it's acute toxicity. China Trop Med. 2011;11(6):719\u201321.","journal-title":"China Trop Med"},{"issue":"1","key":"3364_CR16","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1186\/s12906-017-1955-1","volume":"17","author":"YM Lee","year":"2017","unstructured":"Lee YM, Shon EJ, Kim OS, Kim DS. Effects of Mollugo pentaphylla extract on monosodium urate crystal-induced gouty arthritis in mice. BMC Complement Altern Med. 2017;17(1):447. https:\/\/doi.org\/10.1186\/s12906-017-1955-1.","journal-title":"BMC Complement Altern Med"},{"issue":"5","key":"3364_CR17","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.7150\/thno.40650","volume":"10","author":"A Mariotte","year":"2020","unstructured":"Mariotte A, De Cauwer A, Po C, Abou-Faycal C, Pichot A, Paul N, et al. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1beta as relevant therapy for gout patients. Theranostics. 2020;10(5):2158\u201371. https:\/\/doi.org\/10.7150\/thno.40650.","journal-title":"Theranostics"},{"issue":"1","key":"3364_CR18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41572-019-0115-y","volume":"5","author":"N Dalbeth","year":"2019","unstructured":"Dalbeth N, Choi HK, Joosten LAB, Khanna PP, Matsuo H, Perez-Ruiz F, et al. Gout. Nat Rev Dis Prime. 2019;5(1):69. https:\/\/doi.org\/10.1038\/s41572-019-0115-y.","journal-title":"Nat Rev Dis Prime"},{"issue":"1","key":"3364_CR19","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s13075-020-02244-6","volume":"22","author":"D Vedder","year":"2020","unstructured":"Vedder D, Gerritsen M, Duvvuri B, van Vollenhoven RF, Nurmohamed MT, Lood C. Neutrophil activation identifies patients with active polyarticular gout. Arthritis Res Ther. 2020;22(1):148. https:\/\/doi.org\/10.1186\/s13075-020-02244-6.","journal-title":"Arthritis Res Ther"},{"issue":"3","key":"3364_CR20","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1080\/14397595.2017.1369924","volume":"28","author":"K Yokose","year":"2018","unstructured":"Yokose K, Sato S, Asano T, Yashiro M, Kobayashi H, Watanabe H, et al. TNF-alpha potentiates uric acid-induced interleukin-1beta (IL-1beta) secretion in human neutrophils. Mod Rheumatol. 2018;28(3):513\u20137. https:\/\/doi.org\/10.1080\/14397595.2017.1369924.","journal-title":"Mod Rheumatol"},{"issue":"9","key":"3364_CR21","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1111\/bph.14967","volume":"177","author":"C Yin","year":"2020","unstructured":"Yin C, Liu B, Wang P, Li X, Li Y, Zheng X, et al. Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis. Br J Pharmacol. 2020;177(9):2042\u201357. https:\/\/doi.org\/10.1111\/bph.14967.","journal-title":"Br J Pharmacol"},{"key":"3364_CR22","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.3389\/fimmu.2018.02305","volume":"9","author":"N Song","year":"2018","unstructured":"Song N, Li T. Regulation of NLRP3 Inflammasome by phosphorylation. Front Immunol. 2018;9:2305. https:\/\/doi.org\/10.3389\/fimmu.2018.02305.","journal-title":"Front Immunol"},{"issue":"1","key":"3364_CR23","doi-asserted-by":"publisher","first-page":"34533","DOI":"10.1038\/srep34533","volume":"6","author":"YH Chung","year":"2016","unstructured":"Chung YH, Kim DH, Lee WW. Monosodium urate crystal-induced pro-interleukin-1beta production is post-transcriptionally regulated via the p38 signaling pathway in human monocytes. Sci Rep. 2016;6(1):34533. https:\/\/doi.org\/10.1038\/srep34533.","journal-title":"Sci Rep"},{"issue":"7081","key":"3364_CR24","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature04516","volume":"440","author":"F Martinon","year":"2006","unstructured":"Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237\u201341. https:\/\/doi.org\/10.1038\/nature04516.","journal-title":"Nature."},{"key":"3364_CR25","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2147\/JIR.S11330","volume":"4","author":"SR Kingsbury","year":"2011","unstructured":"Kingsbury SR, Conaghan PG, McDermott MF. The role of the NLRP3 inflammasome in gout. J Inflamm Res. 2011;4:39\u201349. https:\/\/doi.org\/10.2147\/JIR.S11330.","journal-title":"J Inflamm Res"},{"issue":"1","key":"3364_CR26","first-page":"116","volume":"32","author":"C MN","year":"2012","unstructured":"MN C, Z D, Y Z, GB C. Qualitative and quantitative study of Stephania hainanensis H. S. Lo et Y. Tsoong. Chin J Pharm Anal. 2012;32(1):116\u20139.","journal-title":"Chin J Pharm Anal"},{"key":"3364_CR27","doi-asserted-by":"crossref","first-page":"1303524","DOI":"10.1155\/2020\/1303524","volume":"2020","author":"S Li","year":"2020","unstructured":"Li S, Liu X, Chen X, Bi L. Research Progress on anti-inflammatory effects and mechanisms of alkaloids from Chinese medical herbs. Evid Based Complement Altern Med. 2020;2020:1303524.","journal-title":"Evid Based Complement Altern Med"},{"issue":"2","key":"3364_CR28","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1002\/art.33355","volume":"64","author":"FA Amaral","year":"2012","unstructured":"Amaral FA, Costa VV, Tavares LD, Sachs D, Coelho FM, Fagundes CT, et al. NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B (4) in a murine model of gout. Arthritis Rheum. 2012;64(2):474\u201384. https:\/\/doi.org\/10.1002\/art.33355.","journal-title":"Arthritis Rheum"},{"issue":"11","key":"3364_CR29","doi-asserted-by":"publisher","first-page":"3237","DOI":"10.1002\/art.27667","volume":"62","author":"LA Joosten","year":"2010","unstructured":"Joosten LA, Netea MG, Mylona E, Koenders MI, Malireddi RK, Oosting M, et al. Engagement of fatty acids with toll-like receptor 2 drives interleukin-1beta production via the ASC\/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheum. 2010;62(11):3237\u201348. https:\/\/doi.org\/10.1002\/art.27667.","journal-title":"Arthritis Rheum"},{"issue":"10","key":"3364_CR30","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.1002\/art.38747","volume":"66","author":"LL Reber","year":"2014","unstructured":"Reber LL, Marichal T, Sokolove J, Starkl P, Gaudenzio N, Iwakura Y, et al. Contribution of mast cell-derived interleukin-1beta to uric acid crystal-induced acute arthritis in mice. Arthritis Rheumatol. 2014;66(10):2881\u201391. https:\/\/doi.org\/10.1002\/art.38747.","journal-title":"Arthritis Rheumatol"}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-021-03364-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12906-021-03364-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-021-03364-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T16:10:14Z","timestamp":1725466214000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-021-03364-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3364"],"URL":"https:\/\/doi.org\/10.1186\/s12906-021-03364-5","relation":{},"ISSN":["2662-7671"],"issn-type":[{"value":"2662-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]},"assertion":[{"value":"23 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments that used animals were approved by the Institutional Animal Care and Use Committee of Hainan Medical University (Haikou, China).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that there are no competing interests in the publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"202"}}