Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yong, Chen, Zhang, Zhengchun, Huang, Guoshun, Yang, Yang, Zhu, Yiye, Qian, Leilei, Tian, Fang, Liu, Li, Wu, Qijing, Xu, Zhongchi, Chen, Chong, Zhao, Jing, Gao, Kun, Zhou, Enchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662752/
https://www.ncbi.nlm.nih.gov/pubmed/34899287
http://dx.doi.org/10.3389/fphar.2021.717744
_version_ 1784613505809252352
author Yong, Chen
Zhang, Zhengchun
Huang, Guoshun
Yang, Yang
Zhu, Yiye
Qian, Leilei
Tian, Fang
Liu, Li
Wu, Qijing
Xu, Zhongchi
Chen, Chong
Zhao, Jing
Gao, Kun
Zhou, Enchao
author_facet Yong, Chen
Zhang, Zhengchun
Huang, Guoshun
Yang, Yang
Zhu, Yiye
Qian, Leilei
Tian, Fang
Liu, Li
Wu, Qijing
Xu, Zhongchi
Chen, Chong
Zhao, Jing
Gao, Kun
Zhou, Enchao
author_sort Yong, Chen
collection PubMed
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 Online
Article
Text
id pubmed-8662752
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86627522021-12-11 Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology Yong, Chen Zhang, Zhengchun Huang, Guoshun Yang, Yang Zhu, Yiye Qian, Leilei Tian, Fang Liu, Li Wu, Qijing Xu, Zhongchi Chen, Chong Zhao, Jing Gao, Kun Zhou, Enchao Front Pharmacol 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 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. Frontiers Media S.A. 2021-11-26 /pmc/articles/PMC8662752/ /pubmed/34899287 http://dx.doi.org/10.3389/fphar.2021.717744 Text en Copyright © 2021 Yong, Zhang, Huang, Yang, Zhu, Qian, Tian, Liu, Wu, Xu, Chen, Zhao, Gao and Zhou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yong, Chen
Zhang, Zhengchun
Huang, Guoshun
Yang, Yang
Zhu, Yiye
Qian, Leilei
Tian, Fang
Liu, Li
Wu, Qijing
Xu, Zhongchi
Chen, Chong
Zhao, Jing
Gao, Kun
Zhou, Enchao
Exploring the Critical Components and Therapeutic Mechanisms of Perilla frutescens L. in the Treatment of Chronic Kidney Disease via Network Pharmacology
title 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_short 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
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662752/
https://www.ncbi.nlm.nih.gov/pubmed/34899287
http://dx.doi.org/10.3389/fphar.2021.717744
work_keys_str_mv AT yongchen exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT zhangzhengchun exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT huangguoshun exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT yangyang exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT zhuyiye exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT qianleilei exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT tianfang exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT liuli exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT wuqijing exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT xuzhongchi exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT chenchong exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT zhaojing exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT gaokun exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology
AT zhouenchao exploringthecriticalcomponentsandtherapeuticmechanismsofperillafrutescenslinthetreatmentofchronickidneydiseasevianetworkpharmacology