Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolism
IntroductionCurcumin 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-atherosc...
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Frontiers Media S.A.
2025-06-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1632647/full |
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| author | Qianjiao Zhao Qianjiao Zhao Qianjiao Zhao Yueting Zhong Yueting Zhong Yueting Zhong Zheng Li Zheng Li Zheng Li Jia Tang Jia Tang Jia Tang Chao Pi Chao Pi Wenwu Zheng Peng Shi Ying Zuo Jun Jiang Yan Yang Shifeng Chu Yumeng Wei Ling Zhao Ling Zhao Ling Zhao |
| author_facet | Qianjiao Zhao Qianjiao Zhao Qianjiao Zhao Yueting Zhong Yueting Zhong Yueting Zhong Zheng Li Zheng Li Zheng Li Jia Tang Jia Tang Jia Tang Chao Pi Chao Pi Wenwu Zheng Peng Shi Ying Zuo Jun Jiang Yan Yang Shifeng Chu Yumeng Wei Ling Zhao Ling Zhao Ling Zhao |
| author_sort | Qianjiao Zhao |
| collection | DOAJ |
| description | IntroductionCurcumin 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.Method and ResultOil 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.DiscussionCACN136 improves atherosclerotic plaque by regulating macrophage polarization and lipid metabolism, suggesting that CACN136 may be a promising new drug for the treatment of atherosclerosis. |
| format | Article |
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| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-18bde2f569e940f3b2ba91c8278a229e2025-08-20T03:26:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.16326471632647Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolismQianjiao Zhao0Qianjiao Zhao1Qianjiao Zhao2Yueting Zhong3Yueting Zhong4Yueting Zhong5Zheng Li6Zheng Li7Zheng Li8Jia Tang9Jia Tang10Jia Tang11Chao Pi12Chao Pi13Wenwu Zheng14Peng Shi15Ying Zuo16Jun Jiang17Yan Yang18Shifeng Chu19Yumeng Wei20Ling Zhao21Ling Zhao22Ling Zhao23Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Thyroid Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, ChinaTate Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaIntroductionCurcumin 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.Method and ResultOil 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.DiscussionCACN136 improves atherosclerotic plaque by regulating macrophage polarization and lipid metabolism, suggesting that CACN136 may be a promising new drug for the treatment of atherosclerosis.https://www.frontiersin.org/articles/10.3389/fphar.2025.1632647/fullatherosclerosiscurcumin analogmacrophageM1/M2lipid metabolismCACN136 |
| spellingShingle | Qianjiao Zhao Qianjiao Zhao Qianjiao Zhao Yueting Zhong Yueting Zhong Yueting Zhong Zheng Li Zheng Li Zheng Li Jia Tang Jia Tang Jia Tang Chao Pi Chao Pi Wenwu Zheng Peng Shi Ying Zuo Jun Jiang Yan Yang Shifeng Chu Yumeng Wei Ling Zhao Ling Zhao Ling Zhao Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolism Frontiers in Pharmacology atherosclerosis curcumin analog macrophage M1/M2 lipid metabolism CACN136 |
| title | Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolism |
| title_full | Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolism |
| title_fullStr | Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolism |
| title_full_unstemmed | Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolism |
| title_short | Anti atherosclerosis effect and mechanism of a novel curcumin analogue CACN136: regulating macrophage M1/M2 polarization and lipid metabolism |
| title_sort | anti atherosclerosis effect and mechanism of a novel curcumin analogue cacn136 regulating macrophage m1 m2 polarization and lipid metabolism |
| topic | atherosclerosis curcumin analog macrophage M1/M2 lipid metabolism CACN136 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1632647/full |
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