Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway
Abstract Background Dehydrocostus lactone (DHL), a natural sesquiterpene lactone, has significant anti-inflammatory effects and has the potential to inhibit ox-LDL-induced atherosclerosis in laboratory settings. However, the in vivo anti-atherosclerotic effects of DHL and their molecular mechanisms...
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2025-06-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01265-8 |
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| author | Weitao Hong Xiaojia Chen Jiahai Xiao Gengji Chen Jiali Yang Pengfei Zhang Zhizhen Zhang |
| author_facet | Weitao Hong Xiaojia Chen Jiahai Xiao Gengji Chen Jiali Yang Pengfei Zhang Zhizhen Zhang |
| author_sort | Weitao Hong |
| collection | DOAJ |
| description | Abstract Background Dehydrocostus lactone (DHL), a natural sesquiterpene lactone, has significant anti-inflammatory effects and has the potential to inhibit ox-LDL-induced atherosclerosis in laboratory settings. However, the in vivo anti-atherosclerotic effects of DHL and their molecular mechanisms remain unclear. This study explores the anti-atherosclerosis effects of DHL on apolipoprotein E-deficient (ApoE−/−) mice, and the potential mechanism on macrophage-derived foam cells. Methods Blood lipid and arterial plaque were assessed to evaluate the anti-atherosclerosis effect. The levels of inflammatory cytokines were quantified by ELISA assay. A serum metabolomics assay was performed to determine the changes in blood metabolites. A cholesterol efflux assay was used to measure the cholesterol efflux rate. Expression of genes or proteins were examined by qRT-PCR, western blot analysis, or immunofluorescence staining. Results Treatment with DHL greatly reduced blood lipid levels and decreased the formation of atherosclerotic plaques in the aorta in high-fat diet-fed ApoE−/− mice. DHL treatment enhanced cholesterol efflux from foam cells by increasing the expression of ATP-binding cassette (ABC) A1, ABCG1, and peroxisome proliferator-activated receptor gamma (PPAR-γ), both in vitro and in vivo. DHL treatment decreased the levels of IL-1β and TNF-α, elevated IL-10 levels, and promoted the formation of M2 macrophages by inhibiting myeloid differentiation factor 88 and nuclear factor kappa B (NF-κB). Inhibition of TLR2 in foam cells derived from macrophages significantly reduced the inflammatory response and enhanced cholesterol efflux. Conclusion This study demonstrates that treatment with DHL alleviates atherosclerosis by promoting cholesterol efflux and inhibiting inflammation through the TLR2/PPAR-γ/NF-κB signaling pathway. Graphical abstract |
| format | Article |
| id | doaj-art-bb1d2a6ffb41458ab78676ccad7d8969 |
| institution | DOAJ |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-bb1d2a6ffb41458ab78676ccad7d89692025-08-20T03:22:50ZengBMCMolecular Medicine1528-36582025-06-0131111810.1186/s10020-025-01265-8Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathwayWeitao Hong0Xiaojia Chen1Jiahai Xiao2Gengji Chen3Jiali Yang4Pengfei Zhang5Zhizhen Zhang6Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangdong Medical UniversityDepartment of Human Anatomy, School of Basic Medical Sciences, Guangdong Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangdong Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangdong Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangdong Medical UniversityDepartment of Medical Laboratory, Shenzhen Longhua District Central HospitalDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangdong Medical UniversityAbstract Background Dehydrocostus lactone (DHL), a natural sesquiterpene lactone, has significant anti-inflammatory effects and has the potential to inhibit ox-LDL-induced atherosclerosis in laboratory settings. However, the in vivo anti-atherosclerotic effects of DHL and their molecular mechanisms remain unclear. This study explores the anti-atherosclerosis effects of DHL on apolipoprotein E-deficient (ApoE−/−) mice, and the potential mechanism on macrophage-derived foam cells. Methods Blood lipid and arterial plaque were assessed to evaluate the anti-atherosclerosis effect. The levels of inflammatory cytokines were quantified by ELISA assay. A serum metabolomics assay was performed to determine the changes in blood metabolites. A cholesterol efflux assay was used to measure the cholesterol efflux rate. Expression of genes or proteins were examined by qRT-PCR, western blot analysis, or immunofluorescence staining. Results Treatment with DHL greatly reduced blood lipid levels and decreased the formation of atherosclerotic plaques in the aorta in high-fat diet-fed ApoE−/− mice. DHL treatment enhanced cholesterol efflux from foam cells by increasing the expression of ATP-binding cassette (ABC) A1, ABCG1, and peroxisome proliferator-activated receptor gamma (PPAR-γ), both in vitro and in vivo. DHL treatment decreased the levels of IL-1β and TNF-α, elevated IL-10 levels, and promoted the formation of M2 macrophages by inhibiting myeloid differentiation factor 88 and nuclear factor kappa B (NF-κB). Inhibition of TLR2 in foam cells derived from macrophages significantly reduced the inflammatory response and enhanced cholesterol efflux. Conclusion This study demonstrates that treatment with DHL alleviates atherosclerosis by promoting cholesterol efflux and inhibiting inflammation through the TLR2/PPAR-γ/NF-κB signaling pathway. Graphical abstracthttps://doi.org/10.1186/s10020-025-01265-8Dehydrocostus lactoneAtherosclerosisCholesterol effluxAnti-inflammationToll-like receptor 2 |
| spellingShingle | Weitao Hong Xiaojia Chen Jiahai Xiao Gengji Chen Jiali Yang Pengfei Zhang Zhizhen Zhang Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway Molecular Medicine Dehydrocostus lactone Atherosclerosis Cholesterol efflux Anti-inflammation Toll-like receptor 2 |
| title | Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway |
| title_full | Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway |
| title_fullStr | Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway |
| title_full_unstemmed | Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway |
| title_short | Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway |
| title_sort | dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via tlr2 ppar γ nf κb signaling pathway |
| topic | Dehydrocostus lactone Atherosclerosis Cholesterol efflux Anti-inflammation Toll-like receptor 2 |
| url | https://doi.org/10.1186/s10020-025-01265-8 |
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