Han Sang-Kap, Kim Jeon-Kyung, Park Hee-Seo, Shin Yeun-Jeong, Kim Dong-Hyun
Neurobiota Research Center and Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea.
Chin Med. 2021 Aug 14;16(1):77. doi: 10.1186/s13020-021-00492-5.
Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is frequently used to treat anxiety and depression. Psychiatric disorders including depression are associated with gut dysbiosis. Therefore, to comprehend gut microbiota-involved anti-depressive effect of CSS, we examined its effect on restraint stress (RS)-induced depression and gut dysbiosis in mice METHODS: CSS was extracted with water in boiling water bath and freeze-dried. Anxiety and depression was induced in C57BL/6 mice by exposure to RS. Anxiety- and depression-like behaviors were measured in the light/dark transition and elevated plus maze tasks, forced swimming test, and tail suspension test. Biomarkers were assayed by using the enzyme-linked immunosorbent assay and immunoblotting. The gut microbiota composition was analyzed by Illumina iSeq sequencer.
CSS significantly reduced the RS-induced anxiety- and depression-like behaviors in mice. CSS suppressed the RS-induced activation of NF-κB and expression of interleukin (IL)-6 and increased the RS-suppressed expression of brain-derived neurotrophic factor (BDNF). Furthermore, CSS suppressed the RS-induced IL-6 and corticosterone level in the blood and IL-6 expression and myeloperoxidase activity in the colon. CSS decreased the RS-induced γ-Proteobacteria population in gut microbiota, while the RS-suppressed Lactobacillaceae, Prevotellaceae, and AC160630_f populations increased. Fecal transplantation of vehicle-treated control or RS/CSS-treated mice into RS-exposed mice significantly mitigated RS-induced anxity- and depression-like behaviors, suppressed the NF-κB activation in the hippocampus and colon, and reduced the IL-6 and corticosterone levels in the blood. These fecal microbiota transplantations suppressed RS-induced Desulfovibrionaceae and γ-Proteobacteria populations and increased RS-suppressed Lactobacillaceae and Prevotellaceae poulation in the gut microbiota.
CSS alleviated anxiety and depression by inducing NF-κB-involved BDNF expression through the regulation of gut inflammation and microbiota.
柴胡疏肝散（CSS，在韩语中名为Shiho sogansan）是一种中药，常用于治疗焦虑和抑郁。包括抑郁症在内的精神疾病与肠道菌群失调有关。因此，为了理解柴胡疏肝散涉及肠道微生物群的抗抑郁作用，我们研究了其对小鼠束缚应激（RS）诱导的抑郁和肠道菌群失调的影响。
柴胡疏肝散在沸水浴中用水提取并冻干。通过暴露于束缚应激在C57BL/6小鼠中诱导焦虑和抑郁。在明暗转换和高架十字迷宫任务、强迫游泳试验和悬尾试验中测量焦虑样和抑郁样行为。使用酶联免疫吸附测定和免疫印迹法检测生物标志物。通过Illumina iSeq测序仪分析肠道微生物群组成。
柴胡疏肝散显著降低了小鼠中束缚应激诱导的焦虑样和抑郁样行为。柴胡疏肝散抑制了束缚应激诱导的NF-κB激活和白细胞介素（IL）-6的表达，并增加了束缚应激抑制的脑源性神经营养因子（BDNF）的表达。此外，柴胡疏肝散抑制了束缚应激诱导的血液中IL-6和皮质酮水平以及结肠中IL-6的表达和髓过氧化物酶活性。柴胡疏肝散减少了束缚应激诱导的肠道微生物群中γ-变形菌属种群，而束缚应激抑制的乳杆菌科、普雷沃氏菌科和AC160630_f种群增加。将载体处理的对照或束缚应激/柴胡疏肝散处理的小鼠的粪便移植到暴露于束缚应激的小鼠中，显著减轻了束缚应激诱导的焦虑样和抑郁样行为，抑制了海马体和结肠中的NF-κB激活，并降低了血液中的IL-6和皮质酮水平。这些粪便微生物群移植抑制了束缚应激诱导的脱硫弧菌科和γ-变形菌属种群，并增加了束缚应激抑制的肠道微生物群中乳杆菌科和普雷沃氏菌科种群。
柴胡疏肝散通过调节肠道炎症和微生物群诱导涉及NF-κB的BDNF表达，从而减轻焦虑和抑郁。
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