Abstract
BackgroundChaihu-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 miceMethodsCSS 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.ResultsCSS 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.ConclusionsCSS alleviated anxiety and depression by inducing NF-κB-involved BDNF expression through the regulation of gut inflammation and microbiota.
Highlights
Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is fre‐ quently used to treat anxiety and depression
The excessive secretion of glucocorticoids and inflammatory cytokines suppresses the expression of brain-derived neurotrophic factor (BDNF), which is closely associated with the occurrence of psychiatric disorders including depression through the modulation of neuroplasticity in the brain [8], in the hippocampus and activates the innate and adaptive immune responses in the gastrointestinal tract, resulting in the outbreak of anxiety, depression, gut inflammation, and gut dysbiosis [9,10,11]
CSS alleviated restraint stress (RS)‐induced anxiety and depression in mice First, to decide the dosage of CSS in animal experiments, we investigated the effect of CSS on the RS-induced anxiety and depression in mice
Summary
Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is fre‐ quently used to treat anxiety and depression. Anxiety and depression share a lot of common symptoms Exposure to stressors such as restraint stress and social defeat induces the release of glucocorticoids and adrenaline in the adrenal gland and interleukin (IL)-6 and tumor necrosis factor (TNF)-α in immune cells through the hypothalamo-pituitary-adrenal (HPA) axis [3,4,5]. The excessive secretion of glucocorticoids and inflammatory cytokines suppresses the expression of brain-derived neurotrophic factor (BDNF), which is closely associated with the occurrence of psychiatric disorders including depression through the modulation of neuroplasticity in the brain [8], in the hippocampus and activates the innate and adaptive immune responses in the gastrointestinal tract, resulting in the outbreak of anxiety, depression, gut inflammation, and gut dysbiosis [9,10,11]. Gut dysbiosis is closely connected with the outbreak of systemic diseases such as psychiatric disorder and metabolic syndrome through microbiota-gut-brain (MGB) axis [13,14,15]
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