Zhou Xue-Feng, Zhou Wei-E, Liu Wen-Jing, Luo Min-Jing, Wu Xia-Qing, Wang Ying, Liu Peng, Wen Yu-Min, Li Jia-Lin, Zhao Ting-Ting, Zhang Hao-Jun, Zhao Hai-Ling, Li Ping
Beijing University of Chinese Medicine, Beijing100029, China.
Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing100029, China.
J Transl Int Med. 2021 Jun 18;9(2):98-113. doi: 10.2478/jtim-2021-0020. eCollection 2021 Jun.
HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS.
Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes.
179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20β, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were and . Quercetin and Luteolin were verified to have good binding capability with the hub potential targets through molecular docking.
HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.
黄蛭益肾胶囊（HZYS）是一种保护糖尿病肾病（DKD）患者肾功能的中药专利药物。然而，HZYS的药理机制尚不清楚。本研究将采用网络药理学方法探索HZYS的药理机制。
通过中药系统药理学数据库（TCMSP）和文献检索获取HZYS的化学成分。利用TCMSP和瑞士靶点预测数据库鉴定HZYS的潜在靶点。通过在线人类孟德尔遗传数据库、治疗靶点数据库、基因卡片数据库、DisGeNET数据库和药物银行数据库收集DKD相关的靶基因。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，以进一步探索HZYS治疗DKD的机制。进行分子对接以验证主要化合物与核心基因之间的潜在相互作用。
获得179种活性化合物和620个靶基因，其中571个共同靶点被认为是潜在的治疗靶点。HZYS的前10种主要活性化合物为肝素、槲皮素、山奈酚、木犀草素、14-甲基十五烷酸甲酯、（Z）-11-十六碳烯酸甲酯、17-羟皮质酮、4-孕烯-17α，20β，21-三醇-3，11-二酮、汉黄芩素和羟基蜕皮激素。HZYS治疗DKD的核心信号通路为糖尿病并发症中的PI3K-Akt、MAPK、AGE-RAGE、TNF和凋亡。与这些通路相关的前10个靶基因为 和 。通过分子对接验证了槲皮素和木犀草素与核心潜在靶点 具有良好的结合能力。
HZYS似乎通过调节炎症、氧化应激、凋亡和纤维化信号通路来治疗DKD。本研究为HZYS的进一步研究提供了新的视角。
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