Faculty of Chinese Medicine, Macau University of Science and Technology and State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, Macau, PR China.
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong Province 510632, PR China.
Phytomedicine. 2019 Mar 15;56:261-268. doi: 10.1016/j.phymed.2018.11.010. Epub 2018 Nov 8.
Gualou Xiebai decoction (GLXB), a multi-component herbal formula, has been widely used to treat coronary heart disease (CHD) in China for centuries. Several studies have revealed part of its pharmacological activities, whereas its active compounds and mechanisms of action are still unknown because of its complex composition.
Discover the major active compounds and the pharmacological mechanisms of GLXB by network pharmacology methods.
The main candidate target network was constructed by predicting targets of absorbable chemical compounds of GLXB, collecting therapeutic targets of cardiovascular drugs, constructing target network and layers of screening. Community detection and edge-betweenness calculation were applied to analyze the main candidate target network. Cell viability test, Western blot and flow cytometry were performed to validate the predicted results in cardiomyocytes hypoxia/reoxygenation model.
Five clusters and eight cross-talk targets were found in the main candidate target network. Their functions combined together might explain the multifunctional role of GLXB against CHD. Among the cross-talk targets, ESR1 (Estrogen receptor alpha, ERα) and MAPK14 (Mitogen-activated protein kinase 14, p38) were both drug targets and therapeutic targets whose interaction exhibited the greatest edge-betweenness value, suggesting their crucial role in the protective effect of GLXB. The compounds targeting on ESR1 and MAPK14 were identified as apigenin and 25S-macrostemonoside P respectively which were regard as the major bioactive compounds. The predicted results including the major bioactive compounds, their targets and the synergic effects between them were validated.
This study screened out major bioactive compounds from GLXB and offered a new understanding of the protection mechanism of GLXB against CHD by network pharmacology method and provides a combination strategy to explore mechanisms of action of multi-component drugs from a holistic perspective.
瓜蒌薤白汤（GLXB）是一种多成分的草药配方，几个世纪以来，它在中国被广泛用于治疗冠心病（CHD）。尽管有几项研究揭示了其部分药理活性，但由于其复杂的组成，其活性化合物和作用机制仍不清楚。
通过网络药理学方法发现 GLXB 的主要活性化合物和药理机制。
通过预测 GLXB 可吸收化合物的靶标、收集心血管药物的治疗靶标、构建靶标网络和筛选层，构建主要候选靶标网络。采用社区检测和边介数计算分析主要候选靶标网络。在心肌细胞缺氧/复氧模型中，通过细胞活力试验、Western blot 和流式细胞术验证预测结果。
在主要候选靶标网络中发现了五个簇和八个串扰靶标。它们的功能结合在一起可能解释了 GLXB 对 CHD 的多功能作用。在串扰靶标中，ESR1（雌激素受体α，ERα）和 MAPK14（丝裂原激活蛋白激酶 14，p38）既是药物靶标又是治疗靶标，它们的相互作用表现出最大的边介数值，表明它们在 GLXB 的保护作用中起着至关重要的作用。针对 ESR1 和 MAPK14 的化合物分别被鉴定为芹菜素和 25S-大麦芽苷 P，它们被认为是主要的生物活性化合物。预测结果包括主要生物活性化合物、它们的靶标以及它们之间的协同作用，均得到了验证。
本研究通过网络药理学方法筛选出 GLXB 的主要生物活性化合物，为其防治 CHD 的保护机制提供了新的认识，并为从整体角度探索多成分药物作用机制提供了一种组合策略。
