Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmaco...

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Autores principales: Panpan Hu, Na Sun, Ajab khan, Xinyue Zhang, Panpan Sun, Yaogui Sun, Jianzhong Guo, Xiaozhong Zheng, Wei Yin, Kuohai Fan, Jianzhong Wang, Huizhen Yang, Hongquan Li
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/1f2aab2fbfc64e75a5c88fd51d8b2901
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spelling oai:doaj.org-article:1f2aab2fbfc64e75a5c88fd51d8b29012021-11-06T04:13:54ZNetwork pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury0147-651310.1016/j.ecoenv.2021.112865https://doaj.org/article/1f2aab2fbfc64e75a5c88fd51d8b29012021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321009775https://doaj.org/toc/0147-6513Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.Panpan HuNa SunAjab khanXinyue ZhangPanpan SunYaogui SunJianzhong GuoXiaozhong ZhengWei YinKuohai FanJianzhong WangHuizhen YangHongquan LiElsevierarticleScutellarinZearalenoneGranulosa cell injuryNetwork pharmacologyMolecular dockingEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 227, Iss , Pp 112865- (2021)
institution DOAJ
collection DOAJ
language EN
topic Scutellarin
Zearalenone
Granulosa cell injury
Network pharmacology
Molecular docking
Environmental pollution
TD172-193.5
Environmental sciences
GE1-350
spellingShingle Scutellarin
Zearalenone
Granulosa cell injury
Network pharmacology
Molecular docking
Environmental pollution
TD172-193.5
Environmental sciences
GE1-350
Panpan Hu
Na Sun
Ajab khan
Xinyue Zhang
Panpan Sun
Yaogui Sun
Jianzhong Guo
Xiaozhong Zheng
Wei Yin
Kuohai Fan
Jianzhong Wang
Huizhen Yang
Hongquan Li
Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury
description Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.
format article
author Panpan Hu
Na Sun
Ajab khan
Xinyue Zhang
Panpan Sun
Yaogui Sun
Jianzhong Guo
Xiaozhong Zheng
Wei Yin
Kuohai Fan
Jianzhong Wang
Huizhen Yang
Hongquan Li
author_facet Panpan Hu
Na Sun
Ajab khan
Xinyue Zhang
Panpan Sun
Yaogui Sun
Jianzhong Guo
Xiaozhong Zheng
Wei Yin
Kuohai Fan
Jianzhong Wang
Huizhen Yang
Hongquan Li
author_sort Panpan Hu
title Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury
title_short Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury
title_full Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury
title_fullStr Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury
title_full_unstemmed Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury
title_sort network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury
publisher Elsevier
publishDate 2021
url https://doaj.org/article/1f2aab2fbfc64e75a5c88fd51d8b2901
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