Abstract
Chlorogenic acid (CGA) is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE−/− mice and its potential mechanism. ApoE−/− mice were fed a cholesterol-rich diet without (control) or with CGA (200 and 400 mg/kg) or atorvastatin (4 mg/kg) for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg) reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg) also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL)-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPARγ, LXRα, ABCA1 and ABCG1 as well as the transcriptional activity of PPARγ. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE−/− mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA.
Highlights
Atherosclerosis is a major cause of mortality and morbidity and is the single most important cause of cardiovascular disease (CVD) [1,2]
Transactivation reporter assay further showed that Chlorogenic acid (CGA) increased the transcriptional activity of peroxisome proliferator-activated receptor c (PPARc) in a dose dependent manner (Figure 8). These results suggested that CGA may stimulate cholesterol efflux through upregulating the expression of PPARc, liver X receptor a (LXRa), ABCA1 and ABCG1 and the transcriptional activity of PPARc
Our results showed that CGA (400 mg/kg) significantly reduced atherosclerosis development and prevent aortic dilatation to a similar extent as atorvastatin (Figures 1 and 2) in ApoE2/2 mice
Summary
Atherosclerosis is a major cause of mortality and morbidity and is the single most important cause of cardiovascular disease (CVD) [1,2]. A popular approach for the treatment of atherosclerosis is to reduce plasma lipid levels for example by using statins. As atherosclerosis is considered as a multifactorial inflammatory disease and inflammation, oxidative stress, and macrophage foam cell formation are crucial processes in the development of atherosclerotic plaques [6], optimal therapeutic treatment of atherosclerosis should encompass different approaches. Multiple investigations have demonstrated that inhibition of macrophage foam cell formation by stimulating cholesterol efflux can efficiently prevent atherosclerotic plaque occurrence [8,9,10]. The PPARc-LXRa-ABCA1 pathway has been deemed as an important target for the prevention and treatment of atherosclerosis [10,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
