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Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Curcumin has been found to inhibit atherosclerosis. However, its poor stability and low activity severely limit its further application. To overcome the shortcomings of curcumin, our team successfully designed a novel curcumin analog, CACN136. This study aims to explore the anti-atherosclerosis effects of CACN136 and its mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method and Result<\/jats:title><jats:p>Oil Red O staining results showed that CACN136 significantly improved atherosclerosis plaques in the aorta and aortic root of ApoE-\/- mice. RNA sequencing analysis (RNA-seq) indicated that CACN136 inhibits atherosclerosis by regulating lipid metabolism and inflammation-related pathways. <jats:italic>In vitro<\/jats:italic>, CACN136 significantly upregulates the mRNA and protein expression of iNOS and Arg1 in LPS-induced RAW264.7 cells. In ox-LDL-induced RAW264.7 foam cells, CACN136 significantly reduced free cholesterol and total cholesterol levels, and the levels of ABCA1, CD36, and SRA1 mRNA and protein were significantly altered. <jats:italic>In vivo<\/jats:italic>, CACN136 significantly reduced lipid and inflammatory levels, with superior safety and efficacy compared to the same dose of simvastatin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>CACN136 improves atherosclerotic plaque by regulating macrophage polarization and lipid metabolism, suggesting that CACN136 may be a promising new drug for the treatment of atherosclerosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1632647","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T05:25:08Z","timestamp":1750829108000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1\/M2 polarization and lipid metabolism"],"prefix":"10.3389","volume":"16","author":[{"given":"Qianjiao","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueting","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Pi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifeng","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"154490","DOI":"10.1016\/j.prp.2023.154490","article-title":"NLRP3 inflammasome pathway in atherosclerosis: focusing on the therapeutic potential of non-coding RNAs","volume":"246","author":"Al-Hawary","year":"2023","journal-title":"Pathol. 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