Abstract
Gut dysbiosis is closely connected with the outbreak of psychiatric disorders with colitis. Bifidobacteria-fermented red ginseng (fRG) increases the absorption of ginsenoside Rd and protopanxatriol into the blood in volunteers and mice. fRG and Rd alleviates 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Therefore, to understand the gut microbiota-mediated mechanism of fRG against anxiety/depression, we examined the effects of red ginseng (RG), fRG, ginsenoside Rd, and protopanaxatriol on the occurrence of anxiety/depression, colitis, and gut dysbiosis in mice. Mice with anxiety/depression were prepared by being exposed to two stressors, immobilization stress (IS) or Escherichia coli (EC). Treatment with RG and fRG significantly mitigated the stress-induced anxiety/depression-like behaviors in elevated plus maze, light-dark transition, forced swimming (FST), and tail suspension tasks (TST) and reduced corticosterone levels in the blood. Their treatments also suppressed the stress-induced NF-κB activation and NF-κB+/Iba1+ cell population in the hippocampus, while the brain-derived neurotrophic factor (BDNF) expression and BDNF+/NeuN+ cell population were increased. Furthermore, treatment with RG or fRG suppressed the stress-induced colitis: they suppressed myeloperoxidase activity, NF-κB activation, and NF-κB+/CD11c+ cell population in the colon. In particular, fRG suppressed the EC-induced depression-like behaviors in FST and TST and colitis more strongly than RG. fRG treatment also significantly alleviated the EC-induced NF-κB+/Iba1+ cell population and EC-suppressed BDNF+/NeuN+ cell population in the hippocampus more strongly than RG. RG and fRG alleviated EC-induced gut dysbiosis: they increased Bacteroidetes population and decreased Proteobacteria population. Rd and protopanaxatriol also alleviated EC-induced anxiety/depression and colitis. In conclusion, fRG and its constituents Rd and protopanaxatriol mitigated anxiety/depression and colitis by regulating NF-κB-mediated BDNF expression and gut dysbiosis.
Highlights
Anxiety and depression disorders often co-occur both concurrently and sequentially [1,2].Exposure to stressors such as immobilization and forced swimming stimulates the release of adrenal hormones in the adrenal gland and proinflammatory cytokines in the immune cells through the activation of hypothalamic-pituitary-adrenal (HPA) axis [3,4,5]
To understand the gut microbiota-mediated mechanism of red ginseng (RG) and fermented RG (fRG) against anxiety/depression, we examined the effects of RG, fRG, and their constituents ginsenoside Rd and protopanaxatriol on the immobilization stress (IS)- or Escherichia coli K1 (EC)-induced anxiety/depression, colitis, and gut dysbiosis in mice
In order to understand the difference of the anti-anxiety/depression activity between RG and fRG, we examined the effects of RG and fRG on the IS-induced anxiety/depression in mice (Figure 1A–C)
Summary
Anxiety and depression disorders often co-occur both concurrently and sequentially [1,2]. Exposure to stressors such as immobilization and forced swimming stimulates the release of adrenal hormones in the adrenal gland and proinflammatory cytokines in the immune cells through the activation of hypothalamic-pituitary-adrenal (HPA) axis [3,4,5]. Nutrients 2020, 12, 901 hormones and proinflammatory cytokines accelerates the occurrence of anxiety/depression by suppressing brain-derived neurotrophic factor (BDNF) expression in the brain, gut inflammation and dysbiosis by activating innate and adaptive immunities in the intestine [6,7,8]. Regulating gut dysbiosis can be important for the therapy of psychiatric disorders
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