Abstract
Yindanxinnaotong (YD), a traditional Chinese medicine, has been introduced to clinical medicine for more than a decade, while its pharmacological properties are still not to be well addressed. This report aimed to explore the anti-atherosclerosis properties and underlying mechanisms of YD. We initially performed a computational prediction based on a network pharmacology simulation, which clued YD exerted synergistically anti-atherosclerosis properties by vascular endothelium protection, lipid-lowering, anti-inflammation, and anti-oxidation. These outcomes were then validated in atherosclerosis rats. The experiments provided evidences indicating YD’s contribution in this study included, (1) significantly reduced the severity of atherosclerosis, inhibited reconstruction of the artery wall and regulated the lipid profile; (2) enhanced antioxidant power, strengthened the activity of antioxidant enzymes, and decreased malondialdhyde levels; (3) significantly increased the viability of umbilical vein endothelial cells exposed to oxidative stress due to pretreatment with YD; (4) significantly reduced the level of pro-inflammatory cytokines; (5) significantly down-regulated NF-kB/p65 and up-regulated IkB in the YD-treated groups. Overall, these results demonstrated that YD intervention relieves atherosclerosis through regulating lipids, reducing lipid particle deposition in the endothelial layer of artery, enhancing antioxidant power, and repressing inflammation activity by inhibiting the nuclear factor-kappa B signal pathway.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide, and evidence suggests that half of all CVD cases occur in Asia[1,2]
Our results show that YD and atorvastatin treatment significantly decreased plasma levels of C-reactive protein, tumor necrosis factor alpha (TNF-α ), and IL-1β (Table 3), compared with AS group
Network pharmacology offers a new approach of the drug-target exploring and the potential active ingredients identification in traditional Chinese medicine (TCM) research
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide, and evidence suggests that half of all CVD cases occur in Asia[1,2]. Secondary to lipid deposition in the vessel wall, AS is a chronic inflammatory disease of arteries and oxidative stress participates in its pathogenesis[2,3,4]. (ox-LDL), which is taken up by macrophages in the intima of the vascular wall and leads to foam cell formation. Another leading cause of AS is inflammation. Migrated monocytes mature to macrophages, which swallow lipids and become foam cells, leading to inflammatory gene expression and atheromatic plaque formation[7]. Network biology may aid the exploration of drug targets and identify potential active ingredients in TCM research[14,15]. We applied network target prediction and experimental verification to evaluate the links between herbal ingredients and pharmacological actions
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