{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:03:27Z","timestamp":1759190607692,"version":"3.44.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"Objective<\/jats:title>Tanyu Tongzhi Formula (TTF), a clinically proven empirical prescription, has been utilized to treat atherosclerosis (AS) for decades. This study aimed to investigate the therapeutic mechanisms of TTF against AS by integrating bioinformatics, multi-omics, and experimental validation.<\/jats:p><\/jats:sec>Methods<\/jats:title>The metabolites of TTF in serum were identified using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). Bioinformatics was employed to predict drug targets and mechanisms of action. ApoE\u2212\/\u2212<\/jats:sup> C57BL\/6J mice were fed a 12-week high-fat diet to establish an AS model and were treated with TTF crude extract (2.25\u2005g\/kg\/d) via gavage. Interleukin 6 (IL-6) and interleukin 1\u03b2 (IL-1\u03b2) were measured at weeks 6, 10, and 12. At the 12-week endpoint, aortic plaque formation and liver histopathology were evaluated. Liver transcriptomics and serum-targeted lipid metabolomics were performed to assess TTF's regulatory effects on lipid metabolism. in vitro<\/jats:italic>, peritoneal macrophages (PMs) were pretreated with TTF-containing serum for 1\u2005h before LPS (2\u2005\u00b5g\/ml) stimulation. IL-6 and interleukin 10 (IL-10) mRNA were measured by RT-PCR, while NOD-like receptor thermal protein domain associated protein 3 (NLRP3), IL-1\u03b2, interleukin 18 (IL-18) and IL-6 expression were assessed by Western blot (WB).<\/jats:p><\/jats:sec>Results<\/jats:title>Bioinformatics identified 28 key targets of TTF in AS treatment, primarily associated with inflammation and lipid metabolism. TTF significantly reduced aortic plaque area, attenuated hepatic steatosis, and enhanced plaque collagen content. It decreased the serum levels of lipids and pro-inflammatory mediators (IL-6 and IL-1\u03b2) in AS mice. Sphingolipids are the most significantly different lipids. In LPS-stimulated PMs, TTF suppressed IL-6 mRNA and NLRP3 inflammasome activation while upregulating IL-10 mRNA.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>TTF exerts its anti-atherosclerotic effect through inflammation reduction. These findings provide a scientific basis for its clinical application in AS treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2025.1614525","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:25:20Z","timestamp":1759123520000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tanyu Tongzhi Formula relieves the progression of atherosclerotic plaque through lipid regulation and anti-inflammatory effects"],"prefix":"10.3389","volume":"12","author":[{"given":"Tingting","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shishi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s41572-019-0116-x","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3275","DOI":"10.3390\/biomedicines11123275","article-title":"Intraplaque neovascularization, Cd68+ and Inos2+ macrophage infiltrate intensity are associated with atherothrombosis and intraplaque hemorrhage in severe carotid atherosclerosis","volume":"11","author":"Balmos","year":"2023","journal-title":"Biomedicines"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1111\/jam.14441","article-title":"Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites","volume":"127","author":"Nie","year":"2019","journal-title":"J Appl Microbiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4080","DOI":"10.1002\/ptr.7590","article-title":"Therapeutic potential of traditional Chinese medicine in atherosclerosis: a review","volume":"36","author":"Liu","year":"2022","journal-title":"Phytother Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"855","DOI":"10.16466\/j.issn1005-5509.2017.11.002","article-title":"To discuss the treatment with the pathogenesis of weak yang and stringy yin in golden chamber in atherosclerosis","volume":"41","author":"Li","year":"2017","journal-title":"J Zhejiang Chin Med Univ"},{"key":"B6","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.jep.2018.11.043","article-title":"Compatibility principle in the Tanyu Tongzhi formula revealed by a cell-based analysis","volume":"231","author":"Ma","year":"2019","journal-title":"J Ethnopharmacol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"734589","DOI":"10.3389\/fphar.2021.734589","article-title":"Tanyu Tongzhi formula delays atherosclerotic plaque progression by promoting alternative macrophage activation via Ppar\u03b3 and Akt\/Erk signal pathway in Apoe knock-out mice","volume":"12","author":"Ma","year":"2021","journal-title":"Front Pharmacol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"157122","DOI":"10.1016\/j.phymed.2025.157122","article-title":"The Tanyu Tongzhi formula enhances il-10 expression and macrophage efferocytosis to alleviate atherosclerosis in mice","volume":"146","author":"Wu","year":"2025","journal-title":"Phytomedicine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41569-019-0169-2","article-title":"Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities","volume":"16","author":"B\u00e4ck","year":"2019","journal-title":"Nat Rev Cardiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/s41569-023-00860-8","article-title":"Novel and future lipid-modulating therapies for the prevention of cardiovascular disease","volume":"20","author":"Brandts","year":"2023","journal-title":"Nat Rev Cardiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e131178","DOI":"10.1172\/jci131178","article-title":"Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype","volume":"131","author":"Lecce","year":"2021","journal-title":"J Clin Invest"},{"key":"B12","doi-asserted-by":"publisher","first-page":"109375","DOI":"10.1016\/j.biopha.2019.109375","article-title":"The role of traditional Chinese medicine in the treatment of atherosclerosis through the regulation of macrophage activity","volume":"118","author":"Jian","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"B13","doi-asserted-by":"publisher","first-page":"105168","DOI":"10.1016\/j.phrs.2020.105168","article-title":"Traditional Chinese medicine in cardiovascular drug discovery","volume":"160","author":"Lai-Han Leung","year":"2020","journal-title":"Pharmacol Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"155139","DOI":"10.1016\/j.phymed.2023.155139","article-title":"Targeted intervention of natural medicinal active ingredients and traditional Chinese medicine on epigenetic modification: possible strategies for prevention and treatment of atherosclerosis","volume":"122","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"B15","first-page":"1112","article-title":"Effects of Tanyu Tongzhi granule on Tcm syndrome and Ppar\u03b3 of coronary heart disease","volume":"25","author":"Dai","year":"2010","journal-title":"China J Trad Chin Med Pharm"},{"key":"B16","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41392-022-00955-7","article-title":"Inflammation and atherosclerosis: signaling pathways and therapeutic intervention","volume":"7","author":"Kong","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B17","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1161\/circresaha.121.319822","article-title":"Inflammation resolution: implications for atherosclerosis","volume":"130","author":"Doran","year":"2022","journal-title":"Circ Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1161\/circresaha.121.319077","article-title":"Interleukin-6 signaling and anti-interleukin-6 therapeutics in cardiovascular disease","volume":"128","author":"Ridker","year":"2021","journal-title":"Circ Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3499","DOI":"10.1093\/eurheartj\/ehy310","article-title":"Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the canakinumab anti-inflammatory thrombosis outcomes study (cantos)","volume":"39","author":"Ridker","year":"2018","journal-title":"Eur Heart J"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4092","DOI":"10.1093\/eurheartj\/ehaa659","article-title":"Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the colchicine cardiovascular outcomes trial (colcot)","volume":"41","author":"Bouabdallaoui","year":"2020","journal-title":"Eur Heart J"},{"key":"B21","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1161\/circulationaha.121.058233","article-title":"Long-term efficacy of colchicine in patients with chronic coronary disease: insights from Lodoco2","volume":"145","author":"Opstal","year":"2022","journal-title":"Circulation"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1016\/s0140-6736(21)00520-1","article-title":"Il-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (rescue): a double-blind, randomised, placebo-controlled, phase 2 trial","volume":"397","author":"Ridker","year":"2021","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e2343854","DOI":"10.1001\/jamanetworkopen.2023.43854","article-title":"Plasma ceramides and sphingomyelins and sudden cardiac death in the cardiovascular health study","volume":"6","author":"Bockus","year":"2023","journal-title":"JAMA Netw Open"},{"key":"B24","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/s41586-025-08792-8","article-title":"Sensing ceramides by Cysltr2 and P2ry6 to aggravate atherosclerosis","volume":"641","author":"Zhang","year":"2025","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/s41586-024-07098-5","article-title":"Il-10 constrains sphingolipid metabolism to limit inflammation","volume":"627","author":"York","year":"2024","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/j.bbagen.2016.02.014","article-title":". Inhibition of ceramide de novo synthesis by myriocin produces the double effect of reducing pathological inflammation and exerting antifungal activity against A. fumigatus airways infection","volume":"1860","author":"Caretti","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"B27","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s00018-022-04649-9","article-title":"Deleting interleukin-10 from myeloid cells exacerbates atherosclerosis in Apoe(-\/-) mice","volume":"80","author":"Orecchioni","year":"2022","journal-title":"Cell Mol Life Sci"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1614525\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:25:22Z","timestamp":1759123522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1614525\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":27,"alternative-id":["10.3389\/fcvm.2025.1614525"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2025.1614525","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,29]]},"article-number":"1614525"}}