The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
Department of Neurology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Medicine (Baltimore). 2023 Aug 11;102(32):e34716. doi: 10.1097/MD.0000000000034716.
Silicosis is an incurable chronic disease characterized by lung fibrosis and inflammation. The combination of tetrandrine and Buyang Huanwu Decoction (BYHWD) has a curative effect on silicosis. However, the mechanism of action and the key active constituent in BYHWD are still unclear. The present study employed network pharmacology and molecular docking to determine the mechanism of action and the key active components of BYHWD of Tetrandrine in combination with BYHWD for silicosis. The primary elements and targets of BYHWD were obtained from the Traditional Chinese Medicine Systems Pharmacology and analysis platform. The targets associated with tetrandrine and silicosis were identified and extracted from the Comparative Toxicogenomics Database and GeneCards database. The potential targets for the treatment of silicosis using a combination of Tetrandrine and BYHWD were identified by considering the overlapping targets between compound drugs and silicosis. These targets were then utilized to construct protein-protein interaction networks, compound drug-ingredient-target networks, and perform enrichment analyses. The top 5 active ingredients present in the compound drug-ingredient-target network are tetrandrine, quercetin, luteolin, kaempferol, and beta-carotene. Similarly, the top 6 hub genes in the protein-protein interaction network are FGF2, MMP-9, MMP-1, IL-10, IL-17A, and IL-6. The molecular docking suggested that the active components may easily access the active pocket of the hub gene. The in-silico investigation suggested that quercetin might be the active component in BYHWD responsible for therapeutic effectiveness against silicosis. This study identified the active compound and potential molecular mechanism underlying the therapeutic effects of BYHWD in combination with tetrandrine for treating silicosis. Notably, we found that quercetin may serve as the key compound in BYHWD for the treatment of silicosis.
矽肺是一种不可治愈的慢性疾病，其特征是肺纤维化和炎症。汉防己甲素与补阳还五汤（BYHWD）联合治疗矽肺具有疗效。然而，BYHWD 的作用机制和关键活性成分仍不清楚。本研究采用网络药理学和分子对接技术，确定汉防己甲素与 BYHWD 联合治疗矽肺的作用机制和 BYHWD 的关键活性成分。从中药系统药理学和分析平台中获取 BYHWD 的主要元素和靶点。从比较毒理学基因组学数据库和基因卡数据库中确定与汉防己甲素和矽肺相关的靶点，并从中提取。考虑到复方药物和矽肺之间的重叠靶点，确定了使用汉防己甲素和 BYHWD 联合治疗矽肺的潜在靶点。然后利用这些靶点构建蛋白质-蛋白质相互作用网络、复方药物-成分-靶标网络，并进行富集分析。在复方药物-成分-靶标网络中，排名前 5 的活性成分分别为汉防己甲素、槲皮素、木樨草素、山柰酚和β-胡萝卜素。同样，在蛋白质-蛋白质相互作用网络中，排名前 6 的枢纽基因是 FGF2、MMP-9、MMP-1、IL-10、IL-17A 和 IL-6。分子对接表明，活性成分可能容易进入枢纽基因的活性口袋。计算机模拟研究表明，槲皮素可能是 BYHWD 中治疗矽肺的有效成分。本研究确定了汉防己甲素与 BYHWD 联合治疗矽肺的活性化合物和潜在分子机制。值得注意的是，我们发现槲皮素可能是 BYHWD 治疗矽肺的关键化合物。
