Department of Nephrology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University.
School of Medicine, Xiamen University.
Tohoku J Exp Med. 2022 Dec 16;259(1):37-47. doi: 10.1620/tjem.2022.J088. Epub 2022 Oct 27.
Zhibaidihuang Decoction (ZBDHD) is a traditional Chinese medicine with immense potential to treat IgA nephropathy. However, its core ingredients and representative mechanism remain unclear. In this study, we uncovered the key component and underlying mechanisms of ZBDHD for IgA nephropathy by applying network pharmacology and molecular docking approaches. This was done by first identifying the active ingredients and, subsequently, their corresponding gene targets in ZBDHD with the help of the Traditional Chinese Medicine Systems Pharmacology and analysis platform (TCMSP) database, thereby constructing the drug-compound-target network. The IgA nephropathy-associated genes were then identified using GeneCards, Drugbank, and OMIM databases. The overlapped targets were later obtained to establish Protein-Protein Interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, we performed molecular docking among active compounds and hub genes, and thereby verified the key compound of ZBDHD. The drug-compound-gene network consisted of 289 nodes and 1,113 edges. The top four active ingredients were beta-sitosterol, kaempferol, quercetin and stigmasterol. The top five hub genes in the PPI network were AKT1, ILB1, IL-6, TNF, and TP53. Molecular docking results could demonstrate that there was high affinity among active compounds and the core targets, while quercetin may possibly be the key compound of ZBDHD. We first identified the positive compound and the candidate molecular mechanisms of ZBDHD in an IgA nephropathy treatment and discovered that quercetin might be the core compound of ZBDHD in the treatment of IgA nephropathy.
至宝地黄汤（ZBDHD）是一种具有巨大潜力的中药，可用于治疗 IgA 肾病。然而，其核心成分和代表性机制仍不清楚。在这项研究中，我们应用网络药理学和分子对接方法，揭示了 ZBDHD 治疗 IgA 肾病的关键成分和潜在机制。首先，我们借助中药系统药理学和分析平台（TCMSP）数据库，确定了 ZBDHD 的活性成分及其相应的基因靶点，从而构建了药物-化合物-靶标网络。然后，我们使用 GeneCards、Drugbank 和 OMIM 数据库识别与 IgA 肾病相关的基因。最后，我们获得重叠靶点，建立蛋白质-蛋白质相互作用（PPI）网络、基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。然后，我们在活性化合物和枢纽基因之间进行分子对接，从而验证了 ZBDHD 的关键化合物。药物-化合物-基因网络包含 289 个节点和 1113 条边。前四种活性成分是β-谷甾醇、山奈酚、槲皮素和豆甾醇。PPI 网络中的前五个枢纽基因为 AKT1、ILB1、IL-6、TNF 和 TP53。分子对接结果表明，活性化合物与核心靶标之间存在高度亲和力，而槲皮素可能是 ZBDHD 的关键化合物。我们首次确定了 ZBDHD 治疗 IgA 肾病的阳性化合物和候选分子机制，并发现槲皮素可能是 ZBDHD 治疗 IgA 肾病的核心化合物。
