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Review
. 2024 Nov:134:156012.
doi: 10.1016/j.phymed.2024.156012. Epub 2024 Aug 31.

Microbiota-gut-brain axis: Natural antidepressants molecular mechanism

Yitong Lu  1 , Xiaowen Yu  2 , Zhongling Wang  3 , Linghui Kong  1 , Zhenyuan Jiang  4 , Ruirui Shang  5 , Xia Zhong  6 , Shimeng Lv  1 , Guangheng Zhang  1 , Haonan Gao  1 , Ni Yang  1
Affiliations
Review

Microbiota-gut-brain axis: Natural antidepressants molecular mechanism

Yitong Lu et al. Phytomedicine. 2024 Nov.

Abstract

Background: Major depressive disorder (MDD) is a severe mental health condition characterized by persistent depression, impaired cognition, and reduced activity. Increasing evidence suggests that gut microbiota (GM) imbalance is closely linked to the emergence and advancement of MDD, highlighting the potential significance of regulating the "Microbiota-Gut-Brain" (MGB) axis to impact the development of MDD. Natural products (NPs), characterized by broad biological activities, low toxicity, and multi-target characteristics, offer unique advantages in antidepressant treatment by regulating MGB axis.

Purpose: This review was aimed to explore the intricate relationship between the GM and the brain, as well as host responses, and investigated the mechanisms underlying the MGB axis in MDD development. It also explored the pharmacological mechanisms by which NPs modulate MGB axis to exert antidepressant effects and addressed current research limitations. Additionally, it proposed new strategies for future preclinical and clinical applications in the MDD domain.

Methods: To study the effects and mechanism by which NPs exert antidepressant effects through mediating the MGB axis, data were collected from Web of Science, PubMed, ScienceDirect from initial establishment to March 2024. NPs were classified and summarized by their mechanisms of action.

Results: NPs, such as flavonoids,alkaloids,polysaccharides,saponins, terpenoids, can treat MDD by regulating the MGB axis. Its mechanism includes balancing GM, regulating metabolites and neurotransmitters such as SCAFs, 5-HT, BDNF, inhibiting neuroinflammation, improving neural plasticity, and increasing neurogenesis.

Conclusions: NPs display good antidepressant effects, and have potential value for clinical application in the prevention and treatment of MDD by regulating the MGB axis. However, in-depth study of the mechanisms by which antidepressant medications affect MGB axis will also require considerable effort in clinical and preclinical research, which is essential for the development of effective antidepressant treatments.

Keywords: Antidepressant; Depression; Gut microbiota; Microbiota-gut-brain axis; Molecular mechanism; Natural products.

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Conflict of interest statement

Declaration of competing interest No conflict of interest exists in relation to the submission of this manuscript, and the manuscript has been approved by all the authors for publication. I would like to declare on behalf of myself and my co-authors that the work described is original research that has not been published previously and is not under consideration for publication elsewhere, either in whole or in part. All the listed authors have approved the enclosed manuscript. Figs. 1-4 were created by Figdraw (www.figdraw.com).

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