Abstract
AimsAtherosclerosis is the primary cause of cardiovascular diseases and stroke. The current study evaluated the interventional effects of a naturally occurring compound Notoginsenoside R1 (NR1) on atherosclerosis in ApoE−/− mice.Methods and ResultsThe atherosclerotic lesion was significantly alleviated by NR1 treatment and this attenuation was marked by reduction in lipid deposition, fibrosis and oxidative stress. Increased serum levels of GSH and SOD and decreased level of MDH were observed in NR1-treated ApoE−/− mice. NR1 treatment also significantly decreased the levels of CHO, TG, ox-LDL and increased the level of HDL. Additionally, the levels of inflammatory cytokines including IL-2, IL-6, TNF-α and γ-IFN were markedly reduced in NR1-treated ApoE−/− mice. Furthermore, significantly increased aortic expression of miR-26a, miR-21, miR-126a, miR-132, miR-146 and miR-155 and decreased expression of miR-20a and miR-92a were observed in the vehicle-treated ApoE−/− mice. While NR1 treatment led to a significant reduction in the expression of miR-21, miR-26a, miR-126 and increased expression of miR-20a.ConclusionCollectively, our results demonstrated for the first time the anti-atherosclerotic effects of NR1, which could be in part mediated through its multiple targeting effects on inflammation, oxidative stress, lipid metabolism and microRNA expression. These results therefore justify further evaluation of NR1 as a therapeutic agent treating atherosclerosis.
Highlights
Atherosclerosis is a pathological condition of the large arteries characterized by accumulation of lipids and fibrous lesions
In addition to assessing the interventional effect of Notoginsenoside R1 (NR1) treatment on atherosclerosis and related inflammatory changes and oxidative stress, we further evaluated the effects of NR1 on the expression of miRNAs that are mechanistically associated with atherogenesis
In distinct contrast to that from the vehicle-treated ApoE2/2 mice, atherosclerotic lesion was noted to be alleviated in NR1-treated ApoE2/2 mice (Figure 1c), Further quantification of the atherosclerotic lesion in the aortic root showed that the extent of atherosclerosis lesion was significantly reduced in NR1-treated ApoE2/2 mice compared to that from the vehicle-treated ApoE2/2 mice (12.0964.10% in NR1-treated mice vs. 36.3065.47% in vehicle-treated mice, p = 0.018) (Figure1d)
Summary
Atherosclerosis is a pathological condition of the large arteries characterized by accumulation of lipids and fibrous lesions. The clinical significance of atherosclerosis is heightened by its primary association with the development of cardiovascular and cerebrovascular diseases. Dyslipidemia is of primary importance in the development of atherosclerosis [1]. Atherosclerotic lesions develop from inflammatory and fibroproliferative responses to various insults to the endothelial and smooth muscle cells [1,5]. Among the specific cellular and molecular responses associated with the pathogenesis of atherosclerosis, fundamental roles of inflammation and oxidative stress has been recognized bridging the risk factor and the mechanisms of atherogenesis. Ongoing inflammatory response, increased production of reactive oxygen species (ROS) and oxidation of low-density lipoprotein (LDL) are noted throughout all stages of atherosclerosis [6,7,8]
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.
