基于网络药理学和分子对接探讨桂枝茯苓丸治疗子宫内膜异位症的作用机制

doi:10.5246/jcps.2023.09.058

摘要/Abstract

摘要：

子宫内膜异位症是妇科常见疾病, 严重影响患者的心身健康, 桂枝茯苓丸是中药复方, 对子宫内膜异位症具有积极作用, 但桂枝茯苓丸的作用机制尚不清楚。本研究旨在通过网络药理学和分子对接技术揭示桂枝茯苓丸治疗子宫内膜异位症的可能分子机制。首先, 在TCMSP平台筛选出桂枝茯苓丸活性成分, 利用GeneCards、OMIM、PharmGkb、Disgenet、drugbank、TTD数据库筛选出子宫内膜异位症Endometriosis (EMT)的相关靶点基因, 将两者通过R语言、Cytoscapes和STRING进行汇总分析, 筛选出中药靶基因与疾病相关基因并构建中药调控网络和PPI网络图, 通过R语言进行GO和KEGG富集分析。最后, 以核心基因的蛋白受体和所对应的小分子配体进行分子对接。共筛选出桂枝茯苓丸49个成分和189个(去重复后)预测靶点, EMT靶点1115个(去重复后); 通过比对桂枝茯苓丸和EMT共同靶点, 筛选出80个潜在基因。桂枝茯苓丸与疾病的交集基因的PPI网络包涵1218条边和80个节点, 其核心基因有AKT1、TP53、TNF、IL6等。分子对接结果显示桂枝茯苓丸的核心基因与成分有较好的结合能。

关键词: 桂枝茯苓丸, 子宫内膜异位症, 中医药, 网络药理学, 分子对接

Abstract:

Endometriosis (EMT) is a prevalent gynecological disorder that significantly impacts the physical and mental well-being of patients. Gui Zhi Fu Ling Wan (GZFLW), a Chinese herbal compound, has shown the potential to alleviate the symptoms of EMT. However, the molecular mechanism of action of GZFLW remains unclear. This study aimed to determine the possible molecular mechanism of GZFLW for treating EMT using network pharmacology and molecular docking techniques. Initially, the TCMSP platform was used to screen the active ingredients of GZFLW, while GeneCards, OMIM, PharmGkb, Disgenet, Drugbank, and TTD databases were employed to identify the relevant target genes of EMT. The data were analyzed using R language, Cytoscapes, and STRING, and the traditional Chinese medicine (TCM) regulatory network and protein-protein interaction (PPI) network maps were constructed by screening the TCM target genes and the disease-related genes. The GO and KEGG enrichment analyses were performed using the R language. Finally, molecular docking was performed between the protein receptors of the core genes and the corresponding small-molecule ligands. After de-duplication, a total of 49 ingredients and 189 predicted targets of GZFLW, along with 1115 EMT targets, were screened. Eighty potential genes were identified by comparing the common targets of GZFLW and EMT. The PPI network of the intersecting genes of GZFLW and the disease included 1218 edges and 80 nodes, and the core genes were AKT1, TP53, TNF, and IL6. The molecular docking results showed that the core genes of GZFLW exhibited good binding affinity to the ingredients.

Key words: Gui Zhi Fu Ling Wan, Endometriosis, Traditional Chinese medicine, Network pharmacology, Molecular docking

Supporting:

尚平, 刘琳, 方毅. 基于网络药理学和分子对接探讨桂枝茯苓丸治疗子宫内膜异位症的作用机制[J]. 中国药学(英文版), 2023, 32(9): 704-719.

Ping Shang, Lin Liu, Yi Fang. Investigating the mechanism of action of Gui Zhi Fu Ling Wan in the treatment of endometriosis based on network pharmacology and molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(9): 704-719.

图/表 11

Table 1. The active compounds.

Figure 1. Disease target Venn diagram.

Figure 2. Drug target-disease target Venn diagram.

Figure 3. Drug-molecular-target network diagram.

Figure 4. PPI network.

Figure 5. Eighty intersection targets → eight key targets.

Figure 6. The KEGG enrichment analysis.

Figure 7. The GO enrichment analysis.

Figure 8. The lipid and atherosclerosis signaling pathway.

Table 2. The Libscores of four key targets and their interacting compounds.

Figure 9. The results of the mode of action of active compounds with four target proteins using molecular docking are represented. (A) The mode of action of baicalein with the target ATK1 (PDB ID: 3CQW); (B1–B3) The mode of action of kaempferol, paeoniflorin, and quercetin with the target TNF (PDB ID: 5UUI); (C) The mode of action of paeoniflorin with target IL6 (PDB ID: 1ALU); (D1–D2) The mode of action of baicalei, and quercetin with the target TP53 (PDB ID: 501F).

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