Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology

In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (<i>Panax ginseng</i> C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in...

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Main Authors: Zijing Shang, Meiling Fan, Jingtian Zhang, Zi Wang, Shuang Jiang, Wei Li
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/9/8210
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author Zijing Shang
Meiling Fan
Jingtian Zhang
Zi Wang
Shuang Jiang
Wei Li
author_facet Zijing Shang
Meiling Fan
Jingtian Zhang
Zi Wang
Shuang Jiang
Wei Li
author_sort Zijing Shang
collection DOAJ
description In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (<i>Panax ginseng</i> C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries.
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spelling doaj.art-c5f4b223e97e4446a066050abfd4774c2023-11-17T23:06:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249821010.3390/ijms24098210Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network PharmacologyZijing Shang0Meiling Fan1Jingtian Zhang2Zi Wang3Shuang Jiang4Wei Li5College of Chinese Medicinal Materials, National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Jilin Agricultural University, Changchun 130118, ChinaCollege of Animal Medicine, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Jilin Agricultural University, Changchun 130118, ChinaIn this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (<i>Panax ginseng</i> C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries.https://www.mdpi.com/1422-0067/24/9/8210premature ovarian failureD-galactosered ginsengoxidative stressapoptosisnetwork pharmacology
spellingShingle Zijing Shang
Meiling Fan
Jingtian Zhang
Zi Wang
Shuang Jiang
Wei Li
Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology
International Journal of Molecular Sciences
premature ovarian failure
D-galactose
red ginseng
oxidative stress
apoptosis
network pharmacology
title Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology
title_full Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology
title_fullStr Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology
title_full_unstemmed Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology
title_short Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology
title_sort red ginseng improves d galactose induced premature ovarian failure in mice based on network pharmacology
topic premature ovarian failure
D-galactose
red ginseng
oxidative stress
apoptosis
network pharmacology
url https://www.mdpi.com/1422-0067/24/9/8210
work_keys_str_mv AT zijingshang redginsengimprovesdgalactoseinducedprematureovarianfailureinmicebasedonnetworkpharmacology
AT meilingfan redginsengimprovesdgalactoseinducedprematureovarianfailureinmicebasedonnetworkpharmacology
AT jingtianzhang redginsengimprovesdgalactoseinducedprematureovarianfailureinmicebasedonnetworkpharmacology
AT ziwang redginsengimprovesdgalactoseinducedprematureovarianfailureinmicebasedonnetworkpharmacology
AT shuangjiang redginsengimprovesdgalactoseinducedprematureovarianfailureinmicebasedonnetworkpharmacology
AT weili redginsengimprovesdgalactoseinducedprematureovarianfailureinmicebasedonnetworkpharmacology