{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:19:57Z","timestamp":1791404397640,"version":"4.3.3"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T00:00:00Z","timestamp":1749340800000},"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Calcific aortic valve disease (CAVD) is a common cardiovascular disorder. It is characterized by the thickening, fibrosis, and mineralization of aortic valve leaflets. These pathological changes can progress to heart failure if not managed effectively. Current surgical or transcatheter aortic valve replacement options exist, yet no pharmacotherapy has been established to impede CAVD advancement. Prior research by our team spotlighted the significance of lactate\u2010derived protein lactylation (Kla) in initiating valve calcification. In this study, we aim to uncover the anti\u2010calcification capacity of jatrorrhizine (JAT) and dissect its novel molecular underpinnings. The multi\u2010omics analyses were used to indicate that JAT affects the glycolysis of hVICs, thus exerting a therapeutic effect on CAVD. Then, molecular docking, immunoprecipitation, and site mutation were used to demonstrate that JAT can reduce the lactylation of ALDOA at the K42 site by binding to the lactyltransferases KAT5, thereby affecting its enzymatic stability and downstream metabolic pathways. JAT impeded CAVD by perturbing glycolysis and Kla. Notably, a decline in non\u2010histone Kla modification was linked to JAT inhibition of the osteogenic phenotype. ALDOA Kla, among glycolytic rate\u2010limiting enzymes, is a prime target of JAT anti\u2010calcification action. Crucially, the ALDOA K42la site was correlated with JAT\u2010induced suppression of Runx2 expression. JAT treatment effectively curbed osteogenic differentiation in human aortic valve interstitial cells (hVICs) and mitigated CAVD progression in mice. our findings pioneer the revelation that JAT mitigates calcification by targeting ALDOA K42la to interfere with glycolysis, suggesting its potential as a potent preventative agent against CAVD. JAT alleviates calcific aortic valve disease via interfering with glycolysis targeting ALDOA K42 lactylation.<\/jats:p>","DOI":"10.1002\/ptr.8504","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T01:04:47Z","timestamp":1749431087000},"page":"3212-3224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Jatrorrhizine Alleviates Calcific Aortic Valve Disease via Interfering With Glycolysis Targeting\n                    <scp>ALDOA K42<\/scp>\n                    Lactylation"],"prefix":"10.1002","volume":"39","author":[{"given":"Jiaqin","family":"Wu","sequence":"first","affiliation":[{"name":"National Innovation and Attracting Talents \u201c111\u201d Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University  Chongqing China"},{"name":"School of Pharmacy Hubei University of Chinese Medicine  Wuhan 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