Gut microbiota mediated inflammation, neuroendocrine and neurotrophic functions involved in the antidepressant-like effects of diosgenin in chronic restraint stress

Jun-Ji Cui; Ze-Yun Huang; Yi-Hang Xie; Jun-Bin Wu; Guang-Hui Xu; Cheng-Fu Li; Man-Man Zhang; Li-Tao Yi

doi:10.1016/j.jad.2022.10.045

Gut microbiota mediated inflammation, neuroendocrine and neurotrophic functions involved in the antidepressant-like effects of diosgenin in chronic restraint stress

J Affect Disord. 2023 Jan 15:321:242-252. doi: 10.1016/j.jad.2022.10.045. Epub 2022 Oct 30.

Authors

Jun-Ji Cui¹, Ze-Yun Huang¹, Yi-Hang Xie¹, Jun-Bin Wu¹, Guang-Hui Xu², Cheng-Fu Li³, Man-Man Zhang¹, Li-Tao Yi⁴

Affiliations

¹ Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
² Xiamen Medicine Research Institute, Xiamen 361008, Fujian province, PR China.
³ Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361009, Fujian province, PR China. Electronic address: lichengfu103@126.com.
⁴ Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, PR China; Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, PR China. Electronic address: litaoyi@hqu.edu.cn.

PMID: 36349650
DOI: 10.1016/j.jad.2022.10.045

Abstract

Background: Diosgenin is a well-known steroid saponin possessing neuroprotective activities. However, it is unknown whether diosgenin could alleviate depression-like symptoms.

Methods: The antidepressant-like effect of diosgenin was investigated in mice induced by chronic restraint stress. The effects of diosgenin on behaviors, inflammation, neuroendocrine, neurotrophic function, and gut microbiota were evaluated.

Results: The results showed that diosgenin alleviated the depressive-like behaviors in mice. In addition, diosgenin was found to reduce serum concentrations of proinflammatory cytokines and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Besides, diosgenin could activate hippocampal brain-derived neurotrophic factor (BDNF)/TrkB/ERK/CREB signaling pathway and improve the expression of postsynaptic protein PSD95. Meanwhile, the neurogenesis which was inhibited by chronic restraint stress, was totally reversed by diosgenin. Moreover, diosgenin increased the abundance of phylum Firmicutes and the genus Lactobacillus in stressed mice. The results further showed that diosgenin caused a strong correlation between gut microbiota composition and inflammation, the HPA axis activity, or hippocampus neurotrophic function.

Limitations: Only male mice were used for evaluation in the present study, which limits the understanding of effects of diosgenin on the both sexes. In addition, the results only indicate microbiota at the phylum or genus mediate the regulation of neuroinflammation, neuroendocrine, and neurotrophic function, but does not elucidate how microbiota modulate the systems via their primary or secondary metabolites.

Conclusions: The present study shows that diosgenin exerts the antidepressant activity, which is associated with the enhancement of neurotrophic function and the inhibition of inflammatory and neuroendocrine activities via the regulation of gut microbiota.

Keywords: Antidepressant; Diosgenin; HPA axis; Inflammation; Microbiota; Neurotrophy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antidepressive Agents / pharmacology
Antidepressive Agents / therapeutic use
Diosgenin* / pharmacology
Diosgenin* / therapeutic use
Female
Gastrointestinal Microbiome*
Hypothalamo-Hypophyseal System
Inflammation / drug therapy
Male
Mice
Pituitary-Adrenal System

Substances

Diosgenin
Antidepressive Agents