Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology

Chronic kidney disease (CKD) is a chronic progressive disease that seriously threatens human health. Some patients will continue to progress into the CKD stage 3–5 (also called chronic renal failure), which is mainly manifested by a decline in renal function and multi-system damage. Perilla frutesce...

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Autores principales:	Chen Yong, Zhengchun Zhang, Guoshun Huang, Yang Yang, Yiye Zhu, Leilei Qian, Fang Tian, Li Liu, Qijing Wu, Zhongchi Xu, Chong Chen, Jing Zhao, Kun Gao, Enchao Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Perilla frutescens L. chronic kidney disease network pharmacology luteolin critical component therapeutic mechanism Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/f5cfb78a895c46989714398e62a014a0
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spelling	oai:doaj.org-article:f5cfb78a895c46989714398e62a014a02021-12-01T08:09:16ZExploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology1663-981210.3389/fphar.2021.717744https://doaj.org/article/f5cfb78a895c46989714398e62a014a02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.717744/fullhttps://doaj.org/toc/1663-9812Chronic kidney disease (CKD) is a chronic progressive disease that seriously threatens human health. Some patients will continue to progress into the CKD stage 3–5 (also called chronic renal failure), which is mainly manifested by a decline in renal function and multi-system damage. Perilla frutescens (L.) Britton. (Lamiaceae) is one of the most widely used traditional Chinese medicine (TCM) herbs in CKD, especially in CKD stage 3–5. But its active components and mechanisms are still unclear. In this study, we used network pharmacology to analyze the active components of P. frutescens and the main therapeutic targets for intervention in CKD stage 3–5. Then, the key components were selected for enrichment analysis and identified by high performance liquid chromatograph (HPLC). Finally, we verified the critical components through molecular docking, and in vitro experiments. The results show that 19 main active components of P. frutescens were screened, and 108 targets were intersected with CKD stage 3–5. The PPI network was constructed and found that the core nodes AKT1, TP53, IL6, TNF, and MAPK1 may be key therapeutic targets. Enrichment analysis shows that related targets may be involved in regulating various biological functions, and play a therapeutic role in CKD stage 3–5 by regulating apoptosis, T cell receptor, and PI3K-AKT signaling pathways. Molecular docking indicates that the key active components were well docked with its corresponding targets. Five active components were identified and quantified by HPLC. According to the results, luteolin was selected as the critical component for further verification. In vitro experiments have shown that luteolin can effectively alleviate adriamycin (ADR)-induced renal tubular apoptosis and suppress AKT and p53 phosphorylation. The effects of luteolin to reduce apoptosis may be mediated by inhibiting oxidative stress and downregulating the mitogen-activated protein kinase (MAPK) and p53 pathways. In general, we screened and analyzed the possible active components, therapeutic targets and pathways of P. frutescens for treating CKD. Our findings revealed that luteolin can reduce renal tubular epithelial cell apoptosis and may be the critical component of P. frutescens in the treatment of CKD. It provides references and direction for further research.Chen YongZhengchun ZhangGuoshun HuangYang YangYiye ZhuLeilei QianFang TianLi LiuQijing WuZhongchi XuChong ChenJing ZhaoKun GaoEnchao ZhouFrontiers Media S.A.articlePerilla frutescens L.chronic kidney diseasenetwork pharmacologyluteolincritical componenttherapeutic mechanismTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Perilla frutescens L. chronic kidney disease network pharmacology luteolin critical component therapeutic mechanism Therapeutics. Pharmacology RM1-950
spellingShingle	Perilla frutescens L. chronic kidney disease network pharmacology luteolin critical component therapeutic mechanism Therapeutics. Pharmacology RM1-950 Chen Yong Zhengchun Zhang Guoshun Huang Yang Yang Yiye Zhu Leilei Qian Fang Tian Li Liu Qijing Wu Zhongchi Xu Chong Chen Jing Zhao Kun Gao Enchao Zhou Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology
description	Chronic kidney disease (CKD) is a chronic progressive disease that seriously threatens human health. Some patients will continue to progress into the CKD stage 3–5 (also called chronic renal failure), which is mainly manifested by a decline in renal function and multi-system damage. Perilla frutescens (L.) Britton. (Lamiaceae) is one of the most widely used traditional Chinese medicine (TCM) herbs in CKD, especially in CKD stage 3–5. But its active components and mechanisms are still unclear. In this study, we used network pharmacology to analyze the active components of P. frutescens and the main therapeutic targets for intervention in CKD stage 3–5. Then, the key components were selected for enrichment analysis and identified by high performance liquid chromatograph (HPLC). Finally, we verified the critical components through molecular docking, and in vitro experiments. The results show that 19 main active components of P. frutescens were screened, and 108 targets were intersected with CKD stage 3–5. The PPI network was constructed and found that the core nodes AKT1, TP53, IL6, TNF, and MAPK1 may be key therapeutic targets. Enrichment analysis shows that related targets may be involved in regulating various biological functions, and play a therapeutic role in CKD stage 3–5 by regulating apoptosis, T cell receptor, and PI3K-AKT signaling pathways. Molecular docking indicates that the key active components were well docked with its corresponding targets. Five active components were identified and quantified by HPLC. According to the results, luteolin was selected as the critical component for further verification. In vitro experiments have shown that luteolin can effectively alleviate adriamycin (ADR)-induced renal tubular apoptosis and suppress AKT and p53 phosphorylation. The effects of luteolin to reduce apoptosis may be mediated by inhibiting oxidative stress and downregulating the mitogen-activated protein kinase (MAPK) and p53 pathways. In general, we screened and analyzed the possible active components, therapeutic targets and pathways of P. frutescens for treating CKD. Our findings revealed that luteolin can reduce renal tubular epithelial cell apoptosis and may be the critical component of P. frutescens in the treatment of CKD. It provides references and direction for further research.
format	article
author	Chen Yong Zhengchun Zhang Guoshun Huang Yang Yang Yiye Zhu Leilei Qian Fang Tian Li Liu Qijing Wu Zhongchi Xu Chong Chen Jing Zhao Kun Gao Enchao Zhou
author_facet	Chen Yong Zhengchun Zhang Guoshun Huang Yang Yang Yiye Zhu Leilei Qian Fang Tian Li Liu Qijing Wu Zhongchi Xu Chong Chen Jing Zhao Kun Gao Enchao Zhou
author_sort	Chen Yong
title	Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology
title_short	Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology
title_full	Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology
title_fullStr	Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology
title_full_unstemmed	Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology
title_sort	exploring the critical components and therapeutic mechanisms of perilla frutescens l. in the treatment of chronic kidney disease via network pharmacology
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f5cfb78a895c46989714398e62a014a0
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Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology

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