Li Yang, Peng Ying, Ma Ping, Yang Hanlin, Xiong Haiyan, Wang Mengyue, Peng Chongsheng, Tu Pengfei, Li Xiaobo
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Front Pharmacol. 2018 Aug 21;9:967. doi: 10.3389/fphar.2018.00967. eCollection 2018.
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 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.
越来越多的证据表明，神经精神疾病，如抑郁症，通过肠-脑轴与肠道微生物群有关。肉苁蓉在传统中医中以治疗“肾阳虚”而闻名，近年来已被用于治疗神经退行性疾病。在本研究中，建立了慢性不可预测应激（CUS）诱导的抑郁症模型，以探讨肉苁蓉提取物（CTE）对行为测试、海马体和结肠中的单胺神经递质及神经营养因子、肠道微生物群组成以及短链脂肪酸（SCFA）产生的影响。此外，采用相关性分析来评估肠道微生物群改变、海马体和结肠中神经递质及神经营养因子变化以及SCFA浓度紊乱之间的功能关系。CTE显著改善了CUS大鼠的抑郁样行为。CTE恢复了CUS大鼠大脑中5-羟色胺（5-HT）的水平以及脑源性神经营养因子（BDNF）的表达。CTE处理还可以调节肠道微生物群的相对丰度以及乙酸和己酸的浓度。我们进一步表明，在CUS大鼠中应用CTE导致肠道微生物群组成破坏、海马体神经递质水平和神经活性代谢物SCFA产生之间存在强相关性。总之，这些结果表明CTE通过恢复肠道微生物群的稳态来治疗微生物群-肠-脑轴紊乱引起的抑郁症状，为神经精神药理学领域开辟了新途径。
