Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis

Depression is commonly associated with gastrointestinal (GI) disorders, such as constipation, which can potentially intensify depressive symptoms. The interplay between these conditions is believed to be facilitated by the gut-brain axis, which suggests a complex bidirectional interaction. Current t...

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Main Authors: Yi Chen, Peihua Shen, Qi Li, Shun Seng Ong, Yunzhi Qian, Hai Lu, Ming Li, Tianshu Xu
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S036192302500019X
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author Yi Chen
Peihua Shen
Qi Li
Shun Seng Ong
Yunzhi Qian
Hai Lu
Ming Li
Tianshu Xu
author_facet Yi Chen
Peihua Shen
Qi Li
Shun Seng Ong
Yunzhi Qian
Hai Lu
Ming Li
Tianshu Xu
author_sort Yi Chen
collection DOAJ
description Depression is commonly associated with gastrointestinal (GI) disorders, such as constipation, which can potentially intensify depressive symptoms. The interplay between these conditions is believed to be facilitated by the gut-brain axis, which suggests a complex bidirectional interaction. Current treatments, such as antidepressants and prokinetics, are often associated with side effects and high recurrence rates, highlighting the need for effective treatments targeting both depression and constipation. This study was designed to assess the therapeutic efficacy of electroacupuncture (EA) in conjunction with Tongbian decoction (TB) for the management of both depression and constipation, while also investigating the underlying mechanisms through the lens of the gut-brain axis. Chronic unpredictable mild stress (CUMS) was employed to induce a comorbidity model of depression and constipation in mice, followed by the administration of EA, EA + TB, and fluoxetine (FLX). The findings of the study demonstrated that the antidepressant effects of electroacupuncture (EA) in combination with Tongbian decoction (TB) were more pronounced than those of EA alone. The EA + TB treatment significantly ameliorated depression and anxiety-like behaviors, restored cognitive function, and enhanced gastrointestinal motility in chronic unpredictable mild stress (CUMS) mice. Furthermore, EA + TB reduced intestinal inflammation, restored neuronal morphology, increased the expression of tryptophan hydroxylase 2 (TPH2) in both the prefrontal cortex (PFC) and colon, elevated the serum levels of 5-hydroxytryptophan (5-HTP)—a molecule that acts as a gut-brain connector—and promoted the synthesis and production of serotonin (5-HT) in both the gastrointestinal tract and the brain. Contrastingly, FLX showed limited efficacy in improving constipation. In conclusion, EA + TB regulates the TPH2/5-HT pathway via the gut-brain axis, demonstrating synergistic regulation of the nervous and gastrointestinal systems, with favorable antidepressant and prokinetic effects.
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spelling doaj-art-1d7bcdfea0c44df1af0cfa466a3c54b62025-02-07T04:46:43ZengElsevierBrain Research Bulletin1873-27472025-02-01221111207Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axisYi Chen0Peihua Shen1Qi Li2Shun Seng Ong3Yunzhi Qian4Hai Lu5Ming Li6Tianshu Xu7Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nutrition, University of North Carolina at Chapel Hill, USADepartment of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China; Corresponding authors at: Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China; Corresponding authors at: Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China; Corresponding authors at: Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.Depression is commonly associated with gastrointestinal (GI) disorders, such as constipation, which can potentially intensify depressive symptoms. The interplay between these conditions is believed to be facilitated by the gut-brain axis, which suggests a complex bidirectional interaction. Current treatments, such as antidepressants and prokinetics, are often associated with side effects and high recurrence rates, highlighting the need for effective treatments targeting both depression and constipation. This study was designed to assess the therapeutic efficacy of electroacupuncture (EA) in conjunction with Tongbian decoction (TB) for the management of both depression and constipation, while also investigating the underlying mechanisms through the lens of the gut-brain axis. Chronic unpredictable mild stress (CUMS) was employed to induce a comorbidity model of depression and constipation in mice, followed by the administration of EA, EA + TB, and fluoxetine (FLX). The findings of the study demonstrated that the antidepressant effects of electroacupuncture (EA) in combination with Tongbian decoction (TB) were more pronounced than those of EA alone. The EA + TB treatment significantly ameliorated depression and anxiety-like behaviors, restored cognitive function, and enhanced gastrointestinal motility in chronic unpredictable mild stress (CUMS) mice. Furthermore, EA + TB reduced intestinal inflammation, restored neuronal morphology, increased the expression of tryptophan hydroxylase 2 (TPH2) in both the prefrontal cortex (PFC) and colon, elevated the serum levels of 5-hydroxytryptophan (5-HTP)—a molecule that acts as a gut-brain connector—and promoted the synthesis and production of serotonin (5-HT) in both the gastrointestinal tract and the brain. Contrastingly, FLX showed limited efficacy in improving constipation. In conclusion, EA + TB regulates the TPH2/5-HT pathway via the gut-brain axis, demonstrating synergistic regulation of the nervous and gastrointestinal systems, with favorable antidepressant and prokinetic effects.http://www.sciencedirect.com/science/article/pii/S036192302500019XElectroacupunctureTongbian decoctionCUMSConstipationTPH25-HT
spellingShingle Yi Chen
Peihua Shen
Qi Li
Shun Seng Ong
Yunzhi Qian
Hai Lu
Ming Li
Tianshu Xu
Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis
Brain Research Bulletin
Electroacupuncture
Tongbian decoction
CUMS
Constipation
TPH2
5-HT
title Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis
title_full Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis
title_fullStr Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis
title_full_unstemmed Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis
title_short Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis
title_sort electroacupuncture and tongbian decoction ameliorate cums induced depression and constipation in mice via tph2 5 ht pathway of the gut brain axis
topic Electroacupuncture
Tongbian decoction
CUMS
Constipation
TPH2
5-HT
url http://www.sciencedirect.com/science/article/pii/S036192302500019X
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