Lu Yingdong, Sun Yuchan, Jiang Zhilin, Zhang Dandan, Lin Hongchen, Qu Yi, Shang Chang, Zhao Mingjing, Cui Xiangning
Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
The Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Evid Based Complement Alternat Med. 2020 Sep 16;2020:1219371. doi: 10.1155/2020/1219371. eCollection 2020.
Atherosclerosis (AS) is a chronic progressive disease related to dyslipidemia, inflammation, and oxidative stress. Guanxinshutong capsule (GXST), a traditional Chinese medicine, has been widely used in treating coronary atherosclerotic heart disease, while its mechanism actions on AS are still not to be well addressed. Our present study is aimed to examine the effect of GXST on AS and elucidate the multitarget mechanisms of GXST on AS. Network pharmacology analysis was employed to screen the multitarget mechanisms of GXST on AS. ApoE mice were used to validate these effects. Circulating lipid profile and oxidative stress-related factors were measured by the Elisa kit. Furthermore, the aortic trunk and aortic root were excised for oil red O staining, histopathological and immunohistochemical analysis. We first discovered that GXST was clued to exert synergistically antiatherosclerosis properties including lipid-lowering, anti-inflammation, and antioxidation through the computational prediction based on a network pharmacology simulation. Next, the validation experiments in atherosclerosis mice provided evidence that GXST significantly reduced atherosclerotic lesions, increased collagen deposition, and attenuated LV remodeling to some extent. Mechanistically, GXST modulated lipid profile, downregulated the level of inflammatory cytokines and NF-Bp65. GXST also reduced the activity of oxidative parameter MDA and upregulated the activities of antioxidant enzymes (SOD and GSH) compared with the AS model group. In conclusion, GXST intervention might attenuate atherosclerosis by mechanisms involving reducing lipid deposition, modulating oxidative stress and inflammatory responses, but a larger controlled trial is necessary for confirmation.
动脉粥样硬化（AS）是一种与血脂异常、炎症和氧化应激相关的慢性进行性疾病。冠心舒通胶囊（GXST）作为一种中药，已被广泛用于治疗冠状动脉粥样硬化性心脏病，但其对AS的作用机制仍未得到充分阐明。我们目前的研究旨在探讨GXST对AS的影响，并阐明其对AS的多靶点作用机制。采用网络药理学分析筛选GXST对AS的多靶点作用机制。使用载脂蛋白E（ApoE）小鼠来验证这些作用。通过酶联免疫吸附测定（ELISA）试剂盒检测循环血脂谱和氧化应激相关因子。此外，切除主动脉主干和主动脉根部进行油红O染色、组织病理学和免疫组织化学分析。我们首先发现，基于网络药理学模拟的计算预测表明，GXST可能具有协同抗动脉粥样硬化特性，包括降脂、抗炎和抗氧化。接下来，在动脉粥样硬化小鼠中的验证实验提供了证据，表明GXST显著减少了动脉粥样硬化病变，增加了胶原沉积，并在一定程度上减轻了左心室重塑。机制上，GXST调节血脂谱，下调炎性细胞因子和核因子-κB p65的水平。与AS模型组相比，GXST还降低了氧化参数丙二醛（MDA）的活性，上调了抗氧化酶（超氧化物歧化酶（SOD）和谷胱甘肽（GSH））的活性。总之，GXST干预可能通过减少脂质沉积、调节氧化应激和炎症反应等机制减轻动脉粥样硬化，但需要更大规模的对照试验来证实。
