ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Inflammation Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1632647

This article is part of the Research TopicNew Targets and Strategies for the Prevention and Treatment of Organ Fibrosis, Volume IIIView all 14 articles

Anti Atherosclerosis Effect and Mechanism of A Novel Curcumin Analogue CACN136: Regulating Macrophage M1/M2 Polarization and Lipid Metabolism

Provisionally accepted
Qianjiao ZhaoQianjiao ZhaoYueting ZhongYueting ZhongZheng LiZheng LiJia TangJia TangChao PiChao PiWenwu ZhengWenwu ZhengPeng ShiPeng ShiYing ZuoYing ZuoJun JiangJun JiangYan YangYan YangShifeng ChuShifeng ChuYumeng WeiYumeng WeiLing ZhaoLing Zhao*
  • Southwest Medical University, Luzhou, China

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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. 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. In vitro, 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. In vivo, CACN136 significantly reduced lipid and inflammatory levels, with superior safety and efficacy compared to the same dose of simvastatin. 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.

Keywords: Atherosclerosis, Curcumin analog, macrophage, M1/M2, Lipid Metabolism, CACN136

Received: 21 May 2025; Accepted: 11 Jun 2025.

Copyright: © 2025 Zhao, Zhong, Li, Tang, Pi, Zheng, Shi, Zuo, Jiang, Yang, Chu, Wei and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ling Zhao, Southwest Medical University, Luzhou, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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