Suxiaojiuxin Pill Enhances Atherosclerotic Plaque Stability by Modulating the MMPs/TIMPs Balance in ApoE-deficient Mice

Abstract

: Suxiaojiuxin pill (SX) is a famous Chinese formulated product, which has been used to treat coronary heart disease and angina pectoris in China. This study was carried out to investigate the effect and possible mechanism of SX on the stability of atherosclerotic plaque in ApoE-deficient mice. ApoE-/- mice of 6-8 weeks old were fed with high-fat diet for developing artherosclerosis. After oral administration of SX for 8 weeks, histopathology of aortic plaque was performed by Sudan III and hematoxylin-eosin staining, and muscle protein was detected by Western blotting (WB). The mRNA and proteins associated with aortic plaque stability were detected by reverse transcription-polymerase chain reaction and WB, respectively. SX treatment could not only reduce serum triglyceride level and plaque area but also increase fibrous cap thickness and collagen content compared with the model group. WB results showed that SX could increase α-smooth muscle actin, tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2 protein expression, whereas decrease matrix metalloproteinase 2 (MMP-2) and MMP-9 protein expression. Moreover, SX could upregulate the expression of α-smooth muscle actin mRNA and downregulate the expression of vascular endothelial growth factor mRNA. These results showed that SX could enhance atherosclerotic plaque stability in ApoE-deficient mice. The mechanism may be associated with modulating the MMPs/TIMPs balance.

Enhancement of Functionality and Therapeutic Efficacy of Cell-Based Therapy Using Mesenchymal Stem Cells for Cardiovascular Disease

“…Another natural product, Suxiao jiuxin pill (SJP), consists of two major components, tetramethylpyrazine (TMP) and borneol (BOR), and is a prominent traditional Chinese medicine used to treat acute ischemic heart disease [131,132,133]. SJP has significant effects on oxidative stress and vascular reactivity that may lead to improved blood flow.…”

Atheroprotective Effects and Mechanisms of Postmarketing Chinese Patent Formulas in Atherosclerosis Models: A Systematic Review

“…Among these, five low-risk studies [ 40 , 42 , 43 , 66 , 68 ] used the “random number table” in the assessment of sequence generation, seven high-risk studies [ 24 , 33 , 34 , 49 , 59 , 75 , 76 ] did not report the entry, and the remaining 48 studies had unclear detailed random methods. Although none of the studies mentioned random housing, the outcome measures in the 19 studies [ 20 , 23 , 26 , 27 , 29 , 30 , 34 – 36 , 38 , 41 , 45 , 46 , 48 , 50 , 52 , 59 , 73 , 75 ] were not influenced since the feeding conditions (such as temperature, lighting, and humidity) were described, and the bias was evaluated as low risk. The incomplete outcome data were detected in 27 high-risk articles [ 19 – 21 , 23 , 26 , 32 – 36 , 39 , 45 – 47 , 50 – 53 , 55 , 56 , 60 , 61 , 68 , 74 – 77 ] without any reason or appropriate method for describing the missing data, while 18 articles [ 22 , 24 , 25 , 27 – 31 , 38 , 41 , 49 , 54 , 57 , 64 , 70 – 72 , ...…”

“…Although none of the studies mentioned random housing, the outcome measures in the 19 studies [ 20 , 23 , 26 , 27 , 29 , 30 , 34 – 36 , 38 , 41 , 45 , 46 , 48 , 50 , 52 , 59 , 73 , 75 ] were not influenced since the feeding conditions (such as temperature, lighting, and humidity) were described, and the bias was evaluated as low risk. The incomplete outcome data were detected in 27 high-risk articles [ 19 – 21 , 23 , 26 , 32 – 36 , 39 , 45 – 47 , 50 – 53 , 55 , 56 , 60 , 61 , 68 , 74 – 77 ] without any reason or appropriate method for describing the missing data, while 18 articles [ 22 , 24 , 25 , 27 – 31 , 38 , 41 , 49 , 54 , 57 , 64 , 70 – 72 , 78 ] were unclear of the attrition bias. Although none of the studies provided any protocol, almost all had reported the expected outcome indicators, and most of them were evaluated as the low-risk bias.…”

“…Compound Chuanxiong capsule increased collagen proportion in plaques [ 47 ]. Suxiaojiuxin pill enhanced atherosclerotic plaque stability by increasing SMC, TIMP-1, and TIMP-2 proteins while decreasing MMP-2 and MMP-9 proteins, which might be associated with the mechanism of modulating the MMPs/TIMPs balance [ 50 ]. Both Zhixiong and Guanxinshutong capsules enhanced plaque stability by increasing the content of CPA [ 76 , 78 ].…”

Efficacy of Suxiao Jiuxin Pill on Coronary Heart Disease: A Meta‐Analysis of Randomized Controlled Trials

“…Small doses of suxiao jiuxin pill have been shown to rapidly relieve angina pectoris and improve its symptoms without any obvious side effects. Several reports have suggested that suxiao jiuxin pill helps lower the patients' lipid profile and improve myocardial function [ 10 ]. The main components of suxiao jiuxin pills are borneol and Ligusticum chuanxiong Hort [ 9 , 11 – 15 ].…”