Sun Wanqing, Chen Yuan, Li Miao
Third Intenal Department, Hunan Rehabilitation Hospital, Hunan, China.
The Maternal and Child Health of Liu Yang, Hunan Province, China.
Evid Based Complement Alternat Med. 2022 Apr 22;2022:8786052. doi: 10.1155/2022/8786052. eCollection 2022.
ZhiKe GanCao Decoction (ZKGCD) is a commonly used traditional Chinese medicine in the clinical treatment of intervertebral disc degeneration (IDD). However, its active ingredients and mechanism of action remain unclear. This study aims to propose the systematic mechanism of ZKGCD action on IDD based on network pharmacology, molecular docking, and enrichment analysis.
Firstly, the common target genes between ZKGCD and IDD were identified through relevant databases. Secondly, the protein-protein interaction (PPI) network of common genes was constructed and further analyzed to determine the core active ingredients and key genes. Thirdly, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of common genes were performed. Finally, the stability of the binding between core active ingredients and key genes was verified by molecular docking analysis.
"Intersecting genes-active components" network consists of 154 active ingredients and 133 common genes. The ten key genes are AKT1, TNF, IL6, TP53, IL1B, JUN, CASP3, STAT3, MMP9, and MAPK3. Meanwhile, quercetin (Mol000098), luteolin (Mol000006), and kaempferol (Mol000422) are the most important core active ingredients. The main signal pathways selected by KEGG enrichment analysis includes AGE-RAGE signaling pathway in diabetic complications (hsa04933), TNF signaling pathway (hsa04668), IL-17 signaling pathway (hsa04657), cellular senescence (hsa04218), apoptosis (hsa04210), and PI3K-Akt signaling pathway (hsa04151), which are mainly involved in inflammation, apoptosis, senescence, and autophagy.
This study provides a basis for further elucidating the mechanism of action of ZKGCD in the treatment of IDD and offers a new perspective on the conversion of the active ingredient in ZKGCD into new drugs for treating IDD.
枳壳甘草汤（ZKGCD）是临床治疗椎间盘退变（IDD）常用的中药。然而，其活性成分及作用机制尚不清楚。本研究旨在基于网络药理学、分子对接和富集分析提出ZKGCD治疗IDD的系统作用机制。
首先，通过相关数据库确定ZKGCD与IDD之间的共同靶基因。其次，构建共同基因的蛋白质-蛋白质相互作用（PPI）网络并进一步分析，以确定核心活性成分和关键基因。第三，对共同基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。最后，通过分子对接分析验证核心活性成分与关键基因之间结合的稳定性。
“交集基因-活性成分”网络由154种活性成分和133个共同基因组成。十个关键基因是AKT1、TNF、IL6、TP53、IL1B、JUN、CASP3、STAT3、MMP9和MAPK3。同时，槲皮素（Mol000098）、木犀草素（Mol000006）和山奈酚（Mol000422）是最重要的核心活性成分。KEGG富集分析选择的主要信号通路包括糖尿病并发症中的AGE-RAGE信号通路（hsa04933）、TNF信号通路（hsa04668）、IL-17信号通路（hsa04657）、细胞衰老（hsa04218）、凋亡（hsa04210）和PI3K-Akt信号通路（hsa04151），主要涉及炎症、凋亡、衰老和自噬。
本研究为进一步阐明ZKGCD治疗IDD的作用机制提供了依据，并为将ZKGCD中的活性成分转化为治疗IDD的新药提供了新视角。
