Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder
Objective:Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) is a traditional herbal medicine widely known for its antifatigue and antistress effects, as well as tonifying qi, invigorating spleen and kidney, and tranquilizing the mind. Recent evidence suggests that ASH has a therapeutic effect on...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.900637/full |
| _version_ | 1818489923773136896 |
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| author | Xinyi Gu Xinyi Gu Guanying Zhang Qixue Wang Qixue Wang Jing Song Jing Song Ying Li Ying Li Chenyi Xia Ting Zhang Ting Zhang Li Yang Li Yang Jijia Sun Mingmei Zhou Mingmei Zhou |
| author_facet | Xinyi Gu Xinyi Gu Guanying Zhang Qixue Wang Qixue Wang Jing Song Jing Song Ying Li Ying Li Chenyi Xia Ting Zhang Ting Zhang Li Yang Li Yang Jijia Sun Mingmei Zhou Mingmei Zhou |
| author_sort | Xinyi Gu |
| collection | DOAJ |
| description | Objective:Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) is a traditional herbal medicine widely known for its antifatigue and antistress effects, as well as tonifying qi, invigorating spleen and kidney, and tranquilizing the mind. Recent evidence suggests that ASH has a therapeutic effect on major depressive disorder (MDD), but its mechanism is still unclear. The current study aimed to investigate the effect of ASH on MDD and potential therapeutic mechanisms.Materials and Methods: The chemical compound potential target network was predicted based on network pharmacology. Simultaneously, chronic unpredictable mild stress (CUMS) model mice were orally administrated ASH with three dosages (400, 200, and 100 mg/kg) for 6 weeks, and hepatic metabolomics based on gas chromatography–mass spectrometry (GC–MS) was carried out to identify differential metabolites and related metabolic pathways. Next, the integrated analysis of metabolomics and network pharmacology was applied to find the key target. Finally, molecular docking technology was employed to define the combination of the key target and the corresponding compounds.Results: A total of 13 metabolites and four related metabolic pathways were found in metabolomics analysis. From the combined analysis of network pharmacology and metabolomics, six targets (DAO, MAOA, MAOB, GAA, HK1, and PYGM) are the overlapping targets and two metabolic pathways (glycine, serine, and threonine metabolism and starch and sucrose metabolism) are the most related pathways. Finally, DAO, MAOA, MAOB, GAA, HK1, and PYGM were verified bounding well to their corresponding compounds including isofraxidin, eleutheroside B1, eleutheroside C, quercetin, kaempferol, and acacetin.Conclusion: Based on these results, it was implied that the potential mechanism of ASH on MDD was related to the regulation of metabolism of several excitatory amino acids and carbohydrates, as well as the expression of DAO, MAOA, MAOB, GAA, HK1, and PYGM. |
| first_indexed | 2024-12-10T17:10:21Z |
| format | Article |
| id | doaj.art-18e77c5d9f734cfcacf7e3dde3e51e13 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T17:10:21Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-18e77c5d9f734cfcacf7e3dde3e51e132022-12-22T01:40:19ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.900637900637Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorderXinyi Gu0Xinyi Gu1Guanying Zhang2Qixue Wang3Qixue Wang4Jing Song5Jing Song6Ying Li7Ying Li8Chenyi Xia9Ting Zhang10Ting Zhang11Li Yang12Li Yang13Jijia Sun14Mingmei Zhou15Mingmei Zhou16Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Mathematics and Physics, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaObjective:Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) is a traditional herbal medicine widely known for its antifatigue and antistress effects, as well as tonifying qi, invigorating spleen and kidney, and tranquilizing the mind. Recent evidence suggests that ASH has a therapeutic effect on major depressive disorder (MDD), but its mechanism is still unclear. The current study aimed to investigate the effect of ASH on MDD and potential therapeutic mechanisms.Materials and Methods: The chemical compound potential target network was predicted based on network pharmacology. Simultaneously, chronic unpredictable mild stress (CUMS) model mice were orally administrated ASH with three dosages (400, 200, and 100 mg/kg) for 6 weeks, and hepatic metabolomics based on gas chromatography–mass spectrometry (GC–MS) was carried out to identify differential metabolites and related metabolic pathways. Next, the integrated analysis of metabolomics and network pharmacology was applied to find the key target. Finally, molecular docking technology was employed to define the combination of the key target and the corresponding compounds.Results: A total of 13 metabolites and four related metabolic pathways were found in metabolomics analysis. From the combined analysis of network pharmacology and metabolomics, six targets (DAO, MAOA, MAOB, GAA, HK1, and PYGM) are the overlapping targets and two metabolic pathways (glycine, serine, and threonine metabolism and starch and sucrose metabolism) are the most related pathways. Finally, DAO, MAOA, MAOB, GAA, HK1, and PYGM were verified bounding well to their corresponding compounds including isofraxidin, eleutheroside B1, eleutheroside C, quercetin, kaempferol, and acacetin.Conclusion: Based on these results, it was implied that the potential mechanism of ASH on MDD was related to the regulation of metabolism of several excitatory amino acids and carbohydrates, as well as the expression of DAO, MAOA, MAOB, GAA, HK1, and PYGM.https://www.frontiersin.org/articles/10.3389/fcell.2022.900637/fullAcanthopanax senticosus Harmsmajor depressive disordermetabolomicsnetwork pharmacologymolecule docking |
| spellingShingle | Xinyi Gu Xinyi Gu Guanying Zhang Qixue Wang Qixue Wang Jing Song Jing Song Ying Li Ying Li Chenyi Xia Ting Zhang Ting Zhang Li Yang Li Yang Jijia Sun Mingmei Zhou Mingmei Zhou Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder Frontiers in Cell and Developmental Biology Acanthopanax senticosus Harms major depressive disorder metabolomics network pharmacology molecule docking |
| title | Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder |
| title_full | Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder |
| title_fullStr | Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder |
| title_full_unstemmed | Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder |
| title_short | Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder |
| title_sort | integrated network pharmacology and hepatic metabolomics to reveal the mechanism of acanthopanax senticosus against major depressive disorder |
| topic | Acanthopanax senticosus Harms major depressive disorder metabolomics network pharmacology molecule docking |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.900637/full |
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