Abstract：
BACKGROUND: Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease. The decoction has demonstrated its capability to protect arteries and resist atherosclerosis. Its mechanisms for anti-atherosclerosis effect, nevertheless, remain unknown.
OBJECTIVE: The goal of the present study is to explore the effectiveness of ZSXBGZD acting on atherosclerosis and its key components based on experimental verification and network pharmacology analysis.
METHODS: The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and databases were used to identify chemical components in ZSXBGZD. Network pharmacological analysis and molecular docking were implemented in order to reveal the possible therapeutic targets of ZSXBGZD. To form the model of atherosclerosis, we gave Apolipoprotein E knocked out mice a high-fat diet. H&E staining was performed to observe the effects of ZSXBGZD on atherosclerosis. Immunofluorescence and Western blot were used to investigate whether ZSXBGZD could affect autophagy, apoptosis, AGE-RAGE signaling pathway and other related mechanisms.
RESULTS: In total, 30 core compounds were screened through intersecting UPLC-Q-TOF-MS and the databases. The anti-atherosclerotic effect of ZSXBGZD might relate to the AGE-RAGE signaling pathway via network pharmacology analysis. ZSXBGZD could inhibit apoptosis, activate autophagy and ease inflammation by modifying AGE-RAGE signaling pathway to reduce the area of atherosclerotic plaque.
CONCLUSIONS: ZSXBGZD could treat atherosclerosis by regulating autophagy and apoptosis via adjusting the AGE-RAGE signaling pathway.
OBJECTIVE: The goal of the present study is to explore the effectiveness of ZSXBGZD acting on atherosclerosis and its key components based on experimental verification and network pharmacology analysis.
METHODS: The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and databases were used to identify chemical components in ZSXBGZD. Network pharmacological analysis and molecular docking were implemented in order to reveal the possible therapeutic targets of ZSXBGZD. To form the model of atherosclerosis, we gave Apolipoprotein E knocked out mice a high-fat diet. H&E staining was performed to observe the effects of ZSXBGZD on atherosclerosis. Immunofluorescence and Western blot were used to investigate whether ZSXBGZD could affect autophagy, apoptosis, AGE-RAGE signaling pathway and other related mechanisms.
RESULTS: In total, 30 core compounds were screened through intersecting UPLC-Q-TOF-MS and the databases. The anti-atherosclerotic effect of ZSXBGZD might relate to the AGE-RAGE signaling pathway via network pharmacology analysis. ZSXBGZD could inhibit apoptosis, activate autophagy and ease inflammation by modifying AGE-RAGE signaling pathway to reduce the area of atherosclerotic plaque.
CONCLUSIONS: ZSXBGZD could treat atherosclerosis by regulating autophagy and apoptosis via adjusting the AGE-RAGE signaling pathway.
摘要：
背景：栀石泻白桂枝汤（ZSXBGZD）是一种用于治疗心血管疾病的传统草药，包括动脉粥样硬化和冠心病.汤剂已证明其具有保护动脉和抵抗动脉粥样硬化的能力。其抗动脉粥样硬化作用的机制，然而，仍然未知。
目的：本研究的目的是通过实验验证和网络药理学分析，探讨ZSXBGZD对动脉粥样硬化及其关键成分的作用效果。
方法：超高效液相色谱四极杆飞行时间质谱（UPLC-Q-TOF-MS）和数据库用于鉴定ZSXBGZD中的化学成分。实施网络药理学分析和分子对接以揭示ZSXBGZD的可能治疗靶标。形成动脉粥样硬化模型,我们给敲除载脂蛋白E的小鼠提供高脂肪饮食。进行H&E染色以观察ZSXBGZD对动脉粥样硬化的影响。免疫荧光和Westernblot检测ZSXBGZD是否能影响自噬,凋亡，AGE-RAGE信号通路等相关机制。
结果：总计，通过交叉的UPLC-Q-TOF-MS和数据库筛选30个核心化合物。通过网络药理学分析,ZSXBGZD的抗动脉粥样硬化作用可能与AGE-RAGE信号通路有关。ZSXBGZD可抑制细胞凋亡，通过改变AGE-RAGE信号通路,减少动脉粥样硬化斑块面积,激活自噬,缓解炎症反应。
结论：ZSXBGZD可通过调节AGE-RAGE信号通路调节自噬和凋亡，从而治疗动脉粥样硬化。
目的：本研究的目的是通过实验验证和网络药理学分析，探讨ZSXBGZD对动脉粥样硬化及其关键成分的作用效果。
方法：超高效液相色谱四极杆飞行时间质谱（UPLC-Q-TOF-MS）和数据库用于鉴定ZSXBGZD中的化学成分。实施网络药理学分析和分子对接以揭示ZSXBGZD的可能治疗靶标。形成动脉粥样硬化模型,我们给敲除载脂蛋白E的小鼠提供高脂肪饮食。进行H&E染色以观察ZSXBGZD对动脉粥样硬化的影响。免疫荧光和Westernblot检测ZSXBGZD是否能影响自噬,凋亡，AGE-RAGE信号通路等相关机制。
结果：总计，通过交叉的UPLC-Q-TOF-MS和数据库筛选30个核心化合物。通过网络药理学分析,ZSXBGZD的抗动脉粥样硬化作用可能与AGE-RAGE信号通路有关。ZSXBGZD可抑制细胞凋亡，通过改变AGE-RAGE信号通路,减少动脉粥样硬化斑块面积,激活自噬,缓解炎症反应。
结论：ZSXBGZD可通过调节AGE-RAGE信号通路调节自噬和凋亡，从而治疗动脉粥样硬化。
