Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide
Abstract Depression affects people with multiple adverse outcomes, and the side effects of antidepressants are troubling for depression sufferers. Aromatic drugs have been widely used to relieve symptoms of depression with fewer side effects. Ligustilide (LIG) is the main component of volatile oil i...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32495-7 |
| _version_ | 1827970619457667072 |
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| author | Kun Zhang Chaoguo Zhang Xiuli Teng Ke Wang Mingwei Chen |
| author_facet | Kun Zhang Chaoguo Zhang Xiuli Teng Ke Wang Mingwei Chen |
| author_sort | Kun Zhang |
| collection | DOAJ |
| description | Abstract Depression affects people with multiple adverse outcomes, and the side effects of antidepressants are troubling for depression sufferers. Aromatic drugs have been widely used to relieve symptoms of depression with fewer side effects. Ligustilide (LIG) is the main component of volatile oil in angelica sinensis, exhibiting an excellent anti-depressive effect. However, the mechanisms of the anti-depressive effect of LIG remain unclear. Therefore, this study aimed to explore the mechanisms of LIG exerting an anti-depressive effect. We obtained 12,969 depression-related genes and 204 LIG targets by a network pharmacology approach, which were intersected to get 150 LIG anti-depressive targets. Then, we identified core targets by MCODE, including MAPK3, EGF, MAPK14, CCND1, IL6, CASP3, IL2, MYC, TLR4, AKT1, ESR1, TP53, HIF1A, SRC, STAT3, AR, IL1B, and CREBBP. Functional enrichment analysis of core targets showed a significant association with PI3K/AKT and MAPK signaling pathways. Molecular docking showed strong affinities of LIG with AKT1, MAPK14, and ESR1. Finally, we validated the interactions between these proteins and LIG by molecular dynamics (MD) simulations. In conclusion, this study successfully predicted that LIG exerted an anti-depressive effect through multiple targets, including AKT1, MAPK14, and ESR1, and the pathways of PI3K/AKT and MAPK. The study provides a new strategy to explore the molecular mechanisms of LIG in treating depression. |
| first_indexed | 2024-04-09T18:56:37Z |
| format | Article |
| id | doaj.art-fca3dd00d5fc49a4a68706c107a2b039 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T18:56:37Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fca3dd00d5fc49a4a68706c107a2b0392023-04-09T11:12:53ZengNature PortfolioScientific Reports2045-23222023-04-0113111210.1038/s41598-023-32495-7Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilideKun Zhang0Chaoguo Zhang1Xiuli Teng2Ke Wang3Mingwei Chen4Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Depression affects people with multiple adverse outcomes, and the side effects of antidepressants are troubling for depression sufferers. Aromatic drugs have been widely used to relieve symptoms of depression with fewer side effects. Ligustilide (LIG) is the main component of volatile oil in angelica sinensis, exhibiting an excellent anti-depressive effect. However, the mechanisms of the anti-depressive effect of LIG remain unclear. Therefore, this study aimed to explore the mechanisms of LIG exerting an anti-depressive effect. We obtained 12,969 depression-related genes and 204 LIG targets by a network pharmacology approach, which were intersected to get 150 LIG anti-depressive targets. Then, we identified core targets by MCODE, including MAPK3, EGF, MAPK14, CCND1, IL6, CASP3, IL2, MYC, TLR4, AKT1, ESR1, TP53, HIF1A, SRC, STAT3, AR, IL1B, and CREBBP. Functional enrichment analysis of core targets showed a significant association with PI3K/AKT and MAPK signaling pathways. Molecular docking showed strong affinities of LIG with AKT1, MAPK14, and ESR1. Finally, we validated the interactions between these proteins and LIG by molecular dynamics (MD) simulations. In conclusion, this study successfully predicted that LIG exerted an anti-depressive effect through multiple targets, including AKT1, MAPK14, and ESR1, and the pathways of PI3K/AKT and MAPK. The study provides a new strategy to explore the molecular mechanisms of LIG in treating depression.https://doi.org/10.1038/s41598-023-32495-7 |
| spellingShingle | Kun Zhang Chaoguo Zhang Xiuli Teng Ke Wang Mingwei Chen Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide Scientific Reports |
| title | Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide |
| title_full | Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide |
| title_fullStr | Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide |
| title_full_unstemmed | Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide |
| title_short | Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide |
| title_sort | bioinformatics and computational chemistry approaches to explore the mechanism of the anti depressive effect of ligustilide |
| url | https://doi.org/10.1038/s41598-023-32495-7 |
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