Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation.
Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation.
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姜黄素在顺铂诱导的急性肾损伤中的肾保护作用机制：网络药理学分析和实验验证。
DOI：
10.1080/21655979.2021.2005916
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发表时间：
2021-12
期刊：
影响因子：
4.9
通讯作者：
Yao LJ
中科院分区：
文献类型：
--
作者：
Hui Z;Dong QQ;Shu HP;Tu YC;Liao QQ;Yao LJ
顺铂诱导的急性肾损伤（CP-AKI）是接受CP化疗的患者的严重并发症。然而，目前缺乏针对CP-AKI的有效疗法。姜黄素（Curcumin，CUR）是从姜黄根茎中提取的一种天然多酚，具有肾脏保护作用。然而，CUR在CP-AKI中的作用仍不清楚。本研究旨在通过网络药理学方法与实验验证相结合，探索CP-AKI中CUR的机制。该分析揭示了基于HERB数据库的176个CUR潜在靶标和来自GeneCards，DrugBank和OMIM数据库的1，286个CP-AKI相关靶标。进一步获得了106个CUR抗CP-AKI的共同靶点，这些共同靶点构成了蛋白质-蛋白质相互作用（PPI）网络。此外，使用Cytoscape从PPI网络中筛选核心目标。分子对接显示，CUR显示最好的结合AKT 1。基因本体（GO）分析表明，CUR抗CP-AKI的主要生物学过程包括细胞对化学应激的反应和凋亡调节。京都基因和基因组百科全书（KEGG）途径富集分析表明，PI 3 K-Akt信号传导途径在针对CP-AKI的CUR中最显著地富集。Western blotting和流式细胞仪检测结果表明，CUR通过激活Akt信号通路抑制CP诱导的人肾小管上皮细胞（HK-2）凋亡。总之，我们的研究结果表明，CUR减轻细胞凋亡通过激活Akt信号通路在CP-AKI在体外。这些数据为未来研究CUR治疗CP-AKI的临床应用提供了科学依据。
Cisplatin-induced acute kidney injury (CP-AKI) is a severe complication in patients receiving CP chemotherapy. However, effective therapies for CP-AKI are currently lacking. Curcumin (CUR), a natural polyphenol, is extracted from the rhizome of turmeric and has been reported to have nephroprotective activity. However, the role of CUR in CP-AKI remains unclear. This study aimed to explore the mechanism of CUR in CP-AKI by combining a network pharmacology approach with experimental validations. The analysis revealed 176 potential targets of CUR based on the HERB database and 1,286 related targets of CP-AKI from the GeneCards, DrugBank, and OMIM databases. Further, 106 common targets of CUR against CP-AKI were obtained, and these common targets constructed a protein-protein interaction (PPI) network. In addition, the core targets were screened from the PPI network using Cytoscape. Molecular docking revealed that CUR displayed the best binding to AKT1. Gene Ontology (GO) analysis indicated that the primary biological processes of CUR against CP-AKI included cellular response to chemical stress and apoptotic regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the PI3K-Akt signaling pathway was most significantly enriched in CUR against CP-AKI. Western blotting and flow cytometry showed that CUR inhibited apoptosis induced by CP by activating the Akt signaling pathway in human kidney tubular epithelial cells (HK-2). Altogether, our findings demonstrated that CUR alleviated apoptosis by activating the Akt signaling pathway in CP-AKI in vitro. These data provide a scientific basis for future investigations into the clinical application of CUR against CP-AKI.
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