The effect of beta-sitosterol and its derivatives on depression by the modification of 5-HT, DA and GABA-ergic systems in mice

Yin, Yongxia; Liu, Xiaofeng; Liu, Jinping; Cai, Enbo; Zhao, Yan; Li, Haijun; Zhang, Lianxue; Li, Pingya; Gao, Yugang

doi:10.1039/c7ra11364a

Cited by 26 publications

(14 citation statements)

References 44 publications

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“…We found that 5 R-enriched OTUs which belong to family Lachnospiraceae , were positively correlated with stigmasterol. The antidepressant effects of stigmasterol, and the effects on neurotransmitter systems and mechanisms involved in antidepressant effects have been observed 42 . Stigmasterol was found to be resistant to bacterial saturation or degradation, however, the metabolic mechanisms associated with gut microbiota are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment

et al. 2021

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Depression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. Moreover, we identified 15 serum metabolites responsible for discriminating R and NR group. Those differential metabolites were mainly involved in phospholipid metabolism. Significantly, the bacterial OTUs belonging to family Lachnospiraceae, Helicobacteraceae, and Muribaculaceae formed strong co-occurring relationships with serum metabolites, indicating alternations of gut microbiome and metabolites as potential mediators in efficiency of ESC treatment. Together, our study demonstrated that the alterations of microbial compositions and metabolic functions might be relevant to the different response to ESC, which shed new light in uncovering the mechanisms of differences in efficacy of antidepressants.

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Section: Discussionmentioning

confidence: 99%

Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment

et al. 2021

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“…Meanwhile, β-sitosterol exhibits antidepressant and anxiolytic effects (179) (273), possibly mediated through serotonergic, GABAergic and dopaminergic mechanisms. Furthermore, phytosterols modulate the activity of endogenous steroid receptors.…”

Section: Phytosterol Impact On the Microbiota-gut-brain Axismentioning

confidence: 99%

Gut feelings: the microbiota-gut-brain axis on steroids

Savidge

2022

American Journal of Physiology-Gastrointestinal and Liver Physi

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The intricate connection between central and enteric nervous systems is well established with emerging evidence linking gut microbiota function as a significant new contributor to gut-brain axis signaling. Several microbial signals contribute to altered gut-brain communications, with steroids representing an important biological class that impacts central and enteric nervous system function. Neuroactive steroids contribute pathologically to neurological disorders, including dementia and depression, by modulating the activity of neuroreceptors. However, limited information is available on the influence of neuroactive steroids on the enteric nervous system and gastrointestinal function. In this review, we outline how steroids can modulate enteric nervous system function by focusing on their influence on different receptors that are present in the intestine in health and disease. We also highlight the potential role of the gut microbiota in modulating neuroactive steroid signaling along the gut-brain axis.

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“…On the one hand, a mouse model with vastly increased phytosterol levels from birth did not present any apparent memory or anxiety phenotypes, 49 while, on the other hand, several studies have reported pro-explorative or antidepressant properties of crude or partly purified plant sterols when administered intraperitoneally. [50][51][52] Our findings establish b-sitosterol as the only specific and robust anxiolytic from a battery of closely related phytosterols, providing a possible explanation for the conflicting reports on activities of mixed phytosterol extracts summarized above. Moreover, we show that b-sitosterol can synergize with subtherapeutic doses of the SSRI fluoxetine.…”

Section: Discussionmentioning

confidence: 53%

β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice

Panayotis

Freund

Marvaldi

et al. 2021

Cell Reports Medicine

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The effect of beta-sitosterol and its derivatives on depression by the modification of 5-HT, DA and GABA-ergic systems in mice

Abstract: Beta-sitosterol and its derivatives exhibit antidepressant-like activity mediated by the modification of 5-HT, DA and GABA-ergic systems.

Cited by 26 publications

References 44 publications

Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment

Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment

Gut feelings: the microbiota-gut-brain axis on steroids

β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice

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