Chaihu Guizhi decoction ameliorates depression symptoms in chronic restraint stress-induced depressive rats by regulating gut microbiota and short-chain fatty acids

Dong Peng, Yuying Cheng, Yanlan Chen, Xin Cai, Hanxiao Bao, Xiangmin Pan, Wanyue Ding, Jianping Chen, Pan Li
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Abstract

Chaihu Guizhi decoction (CJY) is a classic formula with antidepressant effects; however, it remains unclear whether the antidepressant mechanism of CJY involves modulation of the gut microbiota and which specific bacterial genera are regulated. The present study investigated the effects of CJY on the gut microbiota in chronic restraint stress (CRS)-induced depressive rats. The results showed that CJY treatment attenuated depressive-like behavior, repaired hippocampal neuronal damage, and increased neurotransmitter levels in CRS-induced depressive rats. CJY reshaped the gut microbiota spectrum by increasing the level of the key bacterial genera that alleviate depression, such as Lactobacillus, while decreasing the level of the key bacterial genera that exacerbate depression, such as Bacteroides, Parabacteroides, and Lachnoclostridium. In addition, CJY restored the gut flora dysbiosis-derived changes in the production of short-chain fatty acids, such as acetic acid, propionic acid, and valeric acid. This study lays the foundation for identifying therapeutic targets for CJY and elucidating its underlying mechanisms from the perspective of the microbiota.

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柴胡桂枝煎剂通过调节肠道微生物群和短链脂肪酸改善慢性束缚应激诱导的抑郁大鼠的抑郁症状
柴胡桂枝煎(CJY)是一种具有抗抑郁作用的经典方剂;然而,柴胡桂枝煎的抗抑郁机制是否涉及对肠道微生物群的调节,以及哪些特定细菌属受到了调节,目前仍不清楚。本研究调查了 CJY 对慢性束缚应激(CRS)诱导的抑郁大鼠肠道微生物群的影响。结果显示,CJY 治疗可减轻 CRS 诱导的抑郁大鼠的抑郁样行为,修复海马神经元损伤,并提高神经递质水平。CJY 重塑了肠道微生物群谱,提高了乳酸杆菌等缓解抑郁的关键细菌属的水平,同时降低了乳酸菌属、副乳酸菌属和拉赫诺梭菌属等加剧抑郁的关键细菌属的水平。此外,CJY 还能恢复肠道菌群失调引起的短链脂肪酸(如乙酸、丙酸和戊酸)生成的变化。这项研究为确定 CJY 的治疗靶点以及从微生物群的角度阐明其潜在机制奠定了基础。
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