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Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJ...

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Autores principales: Qu, Shu-Yue, Li, Xiao-Yue, Heng, Xia, Qi, Yi-Yu, Ge, Ping-Yuan, Ni, Sai-jia, Yao, Zeng-Ying, Guo, Rui, Yang, Nian-Yun, Cao, Yi, Zhang, Qi-Chun, Zhu, Hua-Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970346/
https://www.ncbi.nlm.nih.gov/pubmed/33746756
http://dx.doi.org/10.3389/fphar.2021.619288
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author Qu, Shu-Yue
Li, Xiao-Yue
Heng, Xia
Qi, Yi-Yu
Ge, Ping-Yuan
Ni, Sai-jia
Yao, Zeng-Ying
Guo, Rui
Yang, Nian-Yun
Cao, Yi
Zhang, Qi-Chun
Zhu, Hua-Xu
author_facet Qu, Shu-Yue
Li, Xiao-Yue
Heng, Xia
Qi, Yi-Yu
Ge, Ping-Yuan
Ni, Sai-jia
Yao, Zeng-Ying
Guo, Rui
Yang, Nian-Yun
Cao, Yi
Zhang, Qi-Chun
Zhu, Hua-Xu
author_sort Qu, Shu-Yue
collection PubMed
description Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.
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spelling pubmed-79703462021-03-19 Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics Qu, Shu-Yue Li, Xiao-Yue Heng, Xia Qi, Yi-Yu Ge, Ping-Yuan Ni, Sai-jia Yao, Zeng-Ying Guo, Rui Yang, Nian-Yun Cao, Yi Zhang, Qi-Chun Zhu, Hua-Xu Front Pharmacol Pharmacology Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7970346/ /pubmed/33746756 http://dx.doi.org/10.3389/fphar.2021.619288 Text en Copyright © 2021 Qu, Li, Heng, Qi, Ge, Ni, Yao, Guo, Yang, Cao, Zhang and Zhu. http://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
Qu, Shu-Yue
Li, Xiao-Yue
Heng, Xia
Qi, Yi-Yu
Ge, Ping-Yuan
Ni, Sai-jia
Yao, Zeng-Ying
Guo, Rui
Yang, Nian-Yun
Cao, Yi
Zhang, Qi-Chun
Zhu, Hua-Xu
Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics
title Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics
title_full Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics
title_fullStr Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics
title_full_unstemmed Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics
title_short Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics
title_sort analysis of antidepressant activity of huang-lian jie-du decoction through network pharmacology and metabolomics
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970346/
https://www.ncbi.nlm.nih.gov/pubmed/33746756
http://dx.doi.org/10.3389/fphar.2021.619288
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