Mangiferin inhibits hippocampal NLRP3 inflammasome and exerts antidepressant effects in a chronic mild stress mice model

A growing body of evidence suggests that inflammation may contribute toward the development of major depressive disorder. Mangiferin, a glucosylxanthone from Mangifera indica, exerts a number of biological actions, including anti-inflammatory effects. Although mangiferin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study investigated the effects of mangiferin on behavioral changes and inflammatory responses induced by chronic mild stress (CMS) in mice. We found that treatment with mangiferin for 3 weeks significantly increased the body weight of mice and ameliorated CMS-induced behavioral abnormalities by increasing sucrose consumption, improving locomotor activities, and decreasing the immobility time in the forced-swimming test and tail-suspension test. It also suppressed increased serum corticosterone levels in CMS mice. In response to CMS induction, the NLR family, pyrin domain containing 3 (NLRP3) inflammasome was activated and interleukin (IL)-1 and IL-18 levels were increased in the mouse hippocampus. Mangiferin treatment downregulated the expression of NLRP3, the adaptor protein ASC, and caspase-1, which subsequently reduced the production of IL-1 and IL-18 in CMS mice. In sum, our results indicate that mangiferin exerts antidepressant-like effects in CMS model, possibly by inhibiting IL-1 production and NLRP3 inflammasome expression.