Zuojin pill improves chronic unpredictable stress-induced depression-like behavior and gastrointestinal dysfunction in mice via the theTPH2/5-HT pathway

Yan Wang; Yuzhen Huang; Min Zhao; Lu Yang; Kunhan Su; Hao Wu; Yuting Wang; Qing Chang; Wanli Liu

doi:10.1016/j.phymed.2023.155067

Zuojin pill improves chronic unpredictable stress-induced depression-like behavior and gastrointestinal dysfunction in mice via the theTPH2/5-HT pathway

Phytomedicine. 2023 Nov:120:155067. doi: 10.1016/j.phymed.2023.155067. Epub 2023 Sep 3.

Authors

Yan Wang¹, Yuzhen Huang¹, Min Zhao², Lu Yang¹, Kunhan Su³, Hao Wu³, Yuting Wang¹, Qing Chang¹, Wanli Liu⁴

Affiliations

¹ Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing 210014, China.
² Nanjing University of Chinese Medicine, Nanjing 210023, China.
³ Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing 210014, China.
⁴ Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. Electronic address: njzxjh001@njucm.edu.cn.

PMID: 37716030
DOI: 10.1016/j.phymed.2023.155067

Abstract

Background: The complex bidirectional communication between the gastrointestinal tract and the brain is associated with mental disorders such as depression; serotonin, as a crucial neurotransmitter in the communication system between the central nervous system and the gastrointestinal tract, has effects on regulating gastrointestinal motility and sensation and improving psychosomatic status. Zuojin pill is used as a traditional Chinese medicine formula for the treatment of gastrointestinal disorders. This study explored the effects of Zuojin pill on the improvement of depression and gastrointestinal function in CUMS mice via TPH2 and its mechanism.

Purpose: The aim of this study was to investigate whether Zuojin pill could improve depression and concomitant gastrointestinal dysfunction, and to reveal whether Zuojin pill could work through the regulation of the tryptophan hydroxylase 2 (TPH2) pathway.

Methods: The CUMS model was established to observe the effects of Zuojin pill on depression-like behavior and gastrointestinal function in mice. Nissler staining and HE staining were used to observe the structure of hippocampal neurons and intestinal mucosa respectively. 5-HT levels in serum, hippocampus, and intestinal tissues were measured by ELISA, and TPH2 expression in hippocampus and intestinal nerves was observed by WB and immunofluorescence. In order to investigate the protective effect and mechanism of Zuojin pill on PC12 cells, CORT used an in vitro model to produce PC12 cell damage.

Results: Our study showed that Zuojin pill ameliorated depression-like behavior and gastrointestinal dysfunction in CUMS mice, elevated BDNF, 5-HT, and TPH2 expression in the hippocampus, and restored the ratio of dopaminergic and GABAergic neurons between intestinal muscles. In vitro experiments showed that Zuojin pill exerted a protective effect on neurons by regulating TPH2 ubiquitination and thus inhibiting CORT-induced apoptosis of PC12 cells.

Conclusion: Zuojin pill improves chronic unpredictable stress-induced depression-like behavior and gastrointestinal dysfunction in mice via the TPH2/5-HT pathway. Therefore, TPH2 may be a potential therapeutic target for depression with gastrointestinal dysfunction.

Keywords: CUMS; Depression; Gastrointestinal dysfunction; TPH2; Zuojin pill.

MeSH terms

Animals
Depression / drug therapy
Depression / etiology
Drugs, Chinese Herbal* / pharmacology
Gastrointestinal Diseases* / drug therapy
Gastrointestinal Diseases* / etiology
Humans
Mice
Rats
Serotonin

Substances

zuojin
Serotonin
Drugs, Chinese Herbal