{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:58:08Z","timestamp":1790611088013,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204659"],"award-info":[{"award-number":["82204659"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2021CFB227"],"award-info":[{"award-number":["2021CFB227"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Atractylodin (ATL) has been reported to exert anti\u2010inflammatory effects. Osteogenic changes induced by inflammation in valve interstitial cells (VICs) play a key role in the development of calcified aortic valve disease (CAVD). This study aimed to investigate the anti\u2010calcification effects of ATL on aortic valves. Human VICs (hVICs) were exposed to osteogenic induction medium (OM) containing ATL to investigate cell viability, osteogenic gene and protein expression, and anti\u2010calcification effects. Gas chromatography\u2013mass spectroscopy (GC\u2013MS) metabolomics analysis was used to detect changes in the metabolites of hVICs stimulated with OM before and after ATL administration. The compound\u2010reaction\u2010enzyme\u2010gene network was used to identify drug targets. Gene interference was used to verify the targets. ApoE\u2212\/\u2212 mice fed a high\u2010fat (HF) diet were used to evaluate the inhibition of aortic valve calcification by ATL. Treatment with 20\u2009\u03bcM ATL in OM prevented calcified nodule accumulation and decreases in the gene and protein expression levels of ALP, RUNX2, and IL\u20101\u03b2. Differential metabolite analysis showed that D\u2010mannose was highly associated with the anti\u2010calcification effect of ATL. The addition of D\u2010mannose prevented calcified nodule accumulation and inhibited succinate\u2010mediated HIF\u20101\u03b1 activation and IL\u20101\u03b2 production. The target of ATL was identified as <jats:italic>GLA<\/jats:italic>. Silencing of the <jats:italic>GLA<\/jats:italic> gene (si\u2010GLA) reversed the anti\u2010osteogenic differentiation of ATL. In vivo, ATL ameliorated aortic valve calcification by preventing decreases in GLA expression and the up\u2010regulation of IL\u20101\u03b2 expression synchronously. In conclusion, ATL is a potential drug for the treatment of CAVD by targeting <jats:italic>GLA<\/jats:italic> to regulate D\u2010mannose metabolism, thereby inhibiting succinate\u2010mediated HIF\u20101\u03b1 activation and IL\u20101\u03b2 production.<\/jats:p>","DOI":"10.1002\/ptr.7628","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T05:09:40Z","timestamp":1665032980000},"page":"477-489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Atractylodin targets <scp>GLA<\/scp> to regulate D\u2010mannose metabolism to inhibit osteogenic differentiation of human valve interstitial cells and ameliorate aortic valve calcification"],"prefix":"10.1002","volume":"37","author":[{"given":"Linghang","family":"Qu","sequence":"first","affiliation":[{"name":"College of Pharmacy Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8891-1797","authenticated-orcid":false,"given":"Chunli","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanqing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanju","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyun","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8492-2058","authenticated-orcid":false,"given":"Kang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.9b01163"},{"key":"e_1_2_10_3_1","first-page":"575","article-title":"Recommendations for post\u2010discharge patient follow up after cardiac valve interventions: A position paper","volume":"16","author":"Horstkotte D.","year":"2007","journal-title":"The Journal of Heart Valve Disease"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000890"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2014.1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/00015385.2020.1746053"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4665"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110130"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518000113"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00826"},{"key":"e_1_2_10_11_1","first-page":"189","article-title":"Fabry's disease\u2013a comprehensive review on pathogenesis, diagnosis and treatment","volume":"64","author":"Mahmud H. 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