Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation

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...

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Autores principales:	Zhang Hui, Qing-Qing Dong, Hua-Pan Shu, Yu-Chi Tu, Qian-Qian Liao, Li-Jun Yao
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	cisplatin acute kidney injury curcumin network pharmacology molecular docking akt apoptosis Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/c924f66a20b14719a7486cd499f908e3
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spelling	oai:doaj.org-article:c924f66a20b14719a7486cd499f908e32021-12-01T14:41:00ZMechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation2165-59792165-598710.1080/21655979.2021.2005916https://doaj.org/article/c924f66a20b14719a7486cd499f908e32021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005916https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Cisplatin-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.Zhang HuiQing-Qing DongHua-Pan ShuYu-Chi TuQian-Qian LiaoLi-Jun YaoTaylor & Francis Grouparticlecisplatinacute kidney injurycurcuminnetwork pharmacologymolecular dockingaktapoptosisBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 11041-11056 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cisplatin acute kidney injury curcumin network pharmacology molecular docking akt apoptosis Biotechnology TP248.13-248.65
spellingShingle	cisplatin acute kidney injury curcumin network pharmacology molecular docking akt apoptosis Biotechnology TP248.13-248.65 Zhang Hui Qing-Qing Dong Hua-Pan Shu Yu-Chi Tu Qian-Qian Liao Li-Jun Yao Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation
description	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.
format	article
author	Zhang Hui Qing-Qing Dong Hua-Pan Shu Yu-Chi Tu Qian-Qian Liao Li-Jun Yao
author_facet	Zhang Hui Qing-Qing Dong Hua-Pan Shu Yu-Chi Tu Qian-Qian Liao Li-Jun Yao
author_sort	Zhang Hui
title	Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation
title_short	Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation
title_full	Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation
title_fullStr	Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation
title_full_unstemmed	Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation
title_sort	mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/c924f66a20b14719a7486cd499f908e3
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Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation

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