Abstract

Growing evidence shows that neuropsychiatric disorders, such as depression, are linked with gut microbiome through the gut–brain axis. Cistanches Herba is well known for the treatment of “kidney-yang” deficiency in traditional Chinese medicine (TCM), and has been used for treatment of neurodegenerative diseases in recent years. In this study, chronic unpredictable stress (CUS)-induced depression model was established to explore the impact of Cistanche tubulosa extract (CTE) on behavioral tests, monoamine neurotransmitters and neurotrophic factors in hippocampus and colon, gut microbiota composition, and short-chain fatty acids (SCFAs) production. Moreover, correlation analysis was used to evaluate the functional relationship between altered gut microbiota, changed neurotransmitters and neurotrophins in hippocampus and colon, and disturbed concentration of SCFAs. CTE significantly improved depression-like behaviors in rats under CUS. Brain level of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) expression in CUS rats were restored by CTE. The relative abundance of gut microbiota and the concentrations of acetate and hexanoic acid could also be modulated by CTE treatment. We further showed that the application of CTE in CUS rats led to strong correlation among disrupted gut microbiota composition, hippocampus neurotransmitter levels, and production of neuroactive metabolite SCFAs. Altogether, these results identify CTE as a potential treatment for depressive symptoms by restoring homeostasis of gut microbiota for microbiota–gut–brain axis disorders, opening new avenues in the field of neuropsychopharmacology.

Highlights

  • Cistanches Herba (Rou Cong-Rong in Chinese) is officially recorded as the dried succulent stems of Cistanche deserticola

  • This study evaluated the antidepressant activity of Cistanche tubulosa extract (CTE) in chronic unpredictable stress (CUS) rats, and confirmed the efficacy in in vivo models such as Forced swimming test (FST), sucrose preference test (SPT), open-field test (OFT), and novelty-suppressed feeding test (NSFT), and confirmed the anti-depressive activity of C. tubulosa in CUS rats which is frequently used for the treatment of kidney deficiency, impotence, and female infertility in traditional Chinese medicine (TCM)

  • Among all classes of antidepressants, selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) are correlated with the highest incidence of sexual dysfunction (Montejogonzález et al, 1997; Clayton et al, 2014)

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Summary

Introduction

Cistanches Herba (Rou Cong-Rong in Chinese) is officially recorded as the dried succulent stems of Cistanche deserticola C. Ma) and Cistanche tubulosa (Schrenk) in Chinese Pharmacopoeia Commission (2015). Pharmacological analysis has shown that Cistanches Herba exhibits a broad range of neuroprotective, immunomodulatory, anti-inflammatory, and hepatoprotective activities (Jiang and Tu, 2009; Fu et al, 2017). PhGs have been regarded as the major active components of Cistanches Herba possessing various pharmacological activities, such as neuroprotective, immunomodulatory, antiinflammatory, hepatoprotective, and anti-oxidative, etc. Catalpol and geniposide are two representative iridoids in Cistanches Herba, and they have been found to ameliorate chronic unpredictable stress (CUS)-induced depression-like behavior via restoring hypothalamic–pituitary–adrenal (HPA) axis dysfunctions and catalpol can upregulate brain-derived neurotrophic factor (BDNF) expression (Cai et al, 2015; Wang et al, 2015). The latest publication gives a fresh evidence that Cistanches Herba decoction significantly reduced the immobility period in the mouse tail suspension test, which strongly suggesting Cistanches Herba possesses potential antidepressant-like qualities (Wang D. et al, 2017)

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