Abstract
Dyslipidemia, the commonest cause of cardiovascular disease, leads to lipid deposits on the arterial wall, thereby aggravating atherosclerosis. DSHT (Daeshiho-tang) has long been used as an anti-dyslipidemia agent in oriental medicine. However, the anti-atherosclerotic effects of DSHT have not been fully investigated. Therefore, this study was designed to evaluate whether DSHT could exert beneficial anti-atherosclerotic effects. We fed apolipoprotein E-deficient (ApoE-/-) mice on a high-fat diet and treated them with atorvastatin (AT) or DSHT, or the combination of DSHT and AT for 12 weeks. To determine the role of DSHT, atherosclerotic lesions in the aorta, aortic root, and aortic arch; lipids and apolipoprotein levels in serum; and macrophage polarization markers in aorta tissues were examined. We show here that the DSHT decreased the atherosclerotic plaque ratio in the aortic arch, aorta, and aortic root. DSHT also regulated lipid levels by decreasing the ApoB level and increasing the ApoA1 level. Moreover, DSHT effectively regulated cholesterol metabolism by increasing the levels of PPARγ, ABCA1 and ABCG1, and the LDL receptor genes. We further found that DSHT promoted polarization to the M2 phenotype by increasing the levels of M2 macrophage (ARG1, CD163, and PPARγ) markers. Our data suggested that DSHT enhances the anti-atherosclerotic effect by regulating cholesterol metabolism through the activation of the PPARγ signaling pathway and by promoting anti-inflammatory M2 macrophage polarization.
Highlights
Atherosclerosis is a chronic inflammatory disease characterized by lipid deposition, oxidative stress, foam cell formation, monocyte migration, and inflammatory response [1]
This study aimed to investigate the effects of DSHT alone and in combination with AT, and the potential mechanisms underlying its effect by studying atherosclerotic plaque formation and changes in lipid metabolism and the balance of macrophage polarization in atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice fed with a high-fat diet (HFD)
We examined the effect of DSHT and DSHT + AT on the phenotypic polarization of M1/M2 macrophages
Summary
Atherosclerosis is a chronic inflammatory disease characterized by lipid deposition, oxidative stress, foam cell formation, monocyte migration, and inflammatory response [1]. Because of these characteristics, many studies have focused on the absorption of lipids and inhibition of foam cell formation, which play pivotal roles in the early onset of atherosclerosis. Combination therapy with drugs that can reduce the adverse effects while having properties similar to statins is becoming an increasingly used treatment strategy. Some combinational therapies, such as statin with ezetimibe, can reduce cholesterol absorption in the intestine by targeting the Niemann-Pick C1-like 1 protein. There is a critical need to find new drugs and treatment strategies for effective lipid regulation, with fewer adverse effects and improved safety
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