Wang Qin, Zhen Wenrui, Lippi Giuseppe, Liu Qi
Suzhou Medical College of Soochow University, Suzhou, China.
Department of Nephrology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Transl Androl Urol. 2024 Jan 31;13(1):91-103. doi: 10.21037/tau-23-562. Epub 2024 Jan 23.
Acute kidney injury (AKI) is a devastating clinical syndrome with high mortality rate attributed to lack of effective treatment. The herbal pair of (AR) and (RAS) is a commonly prescribed herbal formula or is added to other traditional Chinese medicine (TCM) prescriptions for the treatment of kidney diseases. AR-RAS has certain protective effects on AKI in experiments, but the relevant mechanisms have yet to be clear. So this study aims to explore the mechanism of action of AR-RAS in AKI by combining network pharmacology and molecular docking methods.
In Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the major AR-RAS chemical components and associated action targets were found and screened. The DrugBank and GeneCards databases were used to find AKI-related targets. The targets that are in close relationship with AKI were obtained from Therapeutic Target database (TTD), Online Mendelian Inheritance in Man (OMIM), and PharmGKB databases. The "herb-active ingredient-target" network was drawn by Cytoscape 3.8.0 software. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to build the protein-protein interaction network. Bioconductor/R was used to examine Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. AR-RAS components and critical targets were docked using the AutoDock Vina program.
A compound-target network, built by screening and analyzing the results, allowed to identify 19 active components and 101 possible therapeutic targets for AKI. The main ingredients were quercetin, kaempferol, 7-o-methylisocronulatol, formononetin and isorhamnetin. The key targets included AKT serine/threonine kinase 1 (AKT1), nuclear receptor coactivator 1 (NCOA1), JUN, estrogen receptor alpha (ESR1) and mitogen-activated protein kinase 8 (MAPK8). These molecules are targeted by pathways such as the calcium signaling route, the tumor necrosis factor (TNF) signaling pathway and the interleukin-17 (IL-17) signaling pathway, as well as the development of T helper 17 cells. Molecular docking demonstrated that AR-active RAS components exhibited strong binding activities to probable targets of AKI.
We described here the potential active ingredients, possible targets responsible for the efficacy of AR-RAS in AKI treatment, providing a theoretical basis for further research.
急性肾损伤（AKI）是一种具有高死亡率的严重临床综合征，原因是缺乏有效的治疗方法。黄芪（AR）和丹参（RAS）这味中药对药是一种常用的中药配方，或被添加到其他中药方剂中用于治疗肾脏疾病。AR-RAS在实验中对AKI有一定的保护作用，但其相关机制尚不清楚。因此，本研究旨在通过结合网络药理学和分子对接方法，探索AR-RAS在AKI中的作用机制。
在中药系统药理学数据库与分析平台（TCMSP）中查找并筛选AR-RAS的主要化学成分及相关作用靶点。利用DrugBank和GeneCards数据库查找AKI相关靶点。从治疗靶点数据库（TTD）、人类孟德尔遗传在线数据库（OMIM）和药物基因组学知识库（PharmGKB）中获取与AKI密切相关的靶点。使用Cytoscape 3.8.0软件绘制“草药-活性成分-靶点”网络。利用搜索相互作用基因/蛋白质的工具（STRING）数据库构建蛋白质-蛋白质相互作用网络。使用Bioconductor/R软件检查基因本体论（GO）功能和京都基因与基因组百科全书（KEGG）通路富集情况。使用AutoDock Vina程序对AR-RAS成分与关键靶点进行对接。
通过对筛选和分析结果构建的化合物-靶点网络，确定了19种活性成分和101个可能的AKI治疗靶点。主要成分包括槲皮素、山奈酚、7-O-甲基异鼠李素、芒柄花素和异鼠李素。关键靶点包括AKT丝氨酸/苏氨酸激酶1（AKT1）、核受体辅激活因子1（NCOA1）、JUN、雌激素受体α（ESR1）和丝裂原活化蛋白激酶8（MAPK8）。这些分子受到钙信号通路、肿瘤坏死因子（TNF）信号通路和白细胞介素-17（IL-17）信号通路等信号通路以及辅助性T细胞17（Th17）细胞发育的影响。分子对接表明，AR活性RAS成分对AKI的可能靶点表现出较强的结合活性。
我们在此描述了AR-RAS治疗AKI潜在的活性成分、可能的靶点，为进一步研究提供了理论依据。
