Daeshiho-tang Attenuates Atherosclerosis by Regulating Cholesterol Metabolism and Inducing M2 Macrophage Polarization

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.

LDL cholesterol-lowering effect of Daeshiho-tang in patients with dyslipidemia: A pilot randomized, double-blind, placebo-controlled trial

“…Hussain et al [ 19 ] reported that DSHT administration in obese mice reduced TC concentration by increasing SREBP2 and LDLR expression, and Iizuka et al [ 20 ] confirmed the increase in SREBP2 and LDLR expression using a human hepatoma cell line with DSHT treatment. On the other hand, an underlying mechanism of DSHT at immune cell level is recently reported that DSHT promoted anti-inflammatory M2 macrophage polarization along with cholesterol control of apoB decrease and LDLR increase [ 21 ]. In terms of HDL-C and apoA1 levels, we observed no significant differences between the two groups.…”

Tackling Atherosclerosis via Selected Nutrition

“… Functional products exhibiting cardioprotective activity found in patent research ([ 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 ]). …”