Ginsenoside compound K inhibits oxidative stress and NLRP3 inflammasome activity in mice exposed to chronic unpredictable mild stress

Abstract

Depression, a mood disorder characterized by persistently low mood and feeling of sadness, has been a more and more serious problem today. NLRP3 (the NACHT, LRR and PYD domainscontaining protein 3) inflammasome-mediated central inflammation is recently considered to contribute to the pathology of depression. Based on previous findings that ginsenoside compound K (CK), a ginsenoside metabolite, exhibited antidepressant effects in rats, here we studied whether the antidepressant effects of CK are associated with inhibiting the oxidative stress, NLRP3 inflammasome or inflammatory cytokine in hippocampus of mice exposed to chronic unpredictable mild stress (CUMS). CK (3, 10 and 30 mg/kg) was intragastrically administered for 4 weeks. The depression-like behaviors, oxidative stress parameters, inflammatory cytokines and NLRP3 expression in the hippocampus were evaluated. The results showed that after 4 weeks of administration, CK (30 mg/kg) alleviated the depressant-like behaviors, including shorter immobility time in both the forced swimming test and the tail suspension test, and increased the sucrose preference. In addition, the levels of IL-1b, IL-18 in the hippocampus were significantly decreased in CK-treated groups. The western blot and immunohistochemistry results revealed that the expression levels of NLRP3 inflammasome components (NLRP3 and cleaved caspase-1) were down-regulated in hippocampus of CK-treated mice. These results demonstrate that the antidepressant effect of CK is, at least partially, associated with suppression of oxidative stressinduced NLRP3 inflammasome activation and inhibition of the release of corresponding inflammatory cytokines in the hippocampus.

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

“…The antidepressant role may be due to regulation of the concentration of monoamine neurotransmitters, enhanced antioxidant capacity, and increased expressions of neuronal growth factor and brain-derived neurotrophic factor in the CNS [ 102 ]. In a follow-up study, the defensive effect of CK on CUMS depression was evaluated by inhibiting oxidative stress, inflammatory cytokines and NLRP3 expression using a mouse model [ 103 ].…”

Antidepressant-like effect of riparin I and riparin II against CUMS-induced neuroinflammation via astrocytes and microglia modulation in mice

“…The mentioned model is widely used, as it develops in animals a depressive-like behavior due to the unpredictable sequence of exposure to stressors. This is a result of neurobiological changes similar to those observed in depressed patients, such as dysfunction of hypothalamic–pituitary–adrenal (HPA) axis, dysregulation in cytokine levels and increased lipid peroxidation (Faria et al , 2014; Xue et al , 2015; Song et al , 2019).…”