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

Abstract

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)-1β 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-1β and IL-18 in CMS mice. In sum, our results indicate that mangiferin exerts antidepressant-like effects in CMS model, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression.

Metabolic profiling of rhizomes of native populations of the strictly endemic Croatian species Iris adriatica

“…Similarly, inhibition of NO release was also reported for 2,4′,6-trihydroxy-4-methoxybenzophenone (25) (Pan et al 2016) which additionally showed DPPH radical scavenging effects (Pan et al 2016) as well as induction of apoptosis in HT-29 colon carcinoma cells (Lay et al 2014). Mangiferin (8), the main xanthone in I. adriatica rhizomes, revealed several activities related to antidiabetic effects, like inhibiting endothelial insulin resistance (Xu et al 2017) or α-glucosidase inhibition (Vo et al 2017) as well as anti-inflammatory and antidepressant action (Cao et al 2017). Irilone (34) was shown to possess α-amylase inhibitory effects which would support antidiabetic action (Ibrahim et al 2017).…”

Salvianolic acid B abolished chronic mild stress‐induced depression through suppressing oxidative stress and neuro‐inflammation via regulating NLRP3 inflammasome activation

“…NLRP3 inflammasome, a multiprotein complex (cytosolic NLRP3, ASC, and cleaved caspace‐1), plays a crucial role in the maturation of pro‐inflammatory cytokines like IL‐1β and TNF‐α during psychological stress which contributes for the pathophysiology of depression (Cao et al, ; Iwata et al, ). Increased activation of NLRP3 inflammasome (protein expression) is detected in major depressive disorder patients as well as in various rodents in CMS model which results in upregulation of various pro‐inflammatory cytokines (Alcocer‐Gómez et al, ; Pan et al, ).…”

“…Increased activation of NLRP3 inflammasome (protein expression) is detected in major depressive disorder patients as well as in various rodents in CMS model which results in upregulation of various pro‐inflammatory cytokines (Alcocer‐Gómez et al, ; Pan, Chen, Zhang, & Kong, ). Hence, any drug which might downregulate the expression of NLRP3 (activation) would be a potent therapeutic drug against depression (Cao et al, ). At present, numerous anti‐depressant drugs like selective serotonin reuptake, monoamine oxidase inhibitors, and tricyclic anti‐depressants are available in the market.…”

Mangiferin inhibits lipopolysaccharide‐induced epithelial‐mesenchymal transition (EMT) and enhances the expression of tumor suppressor gene PER1 in non‐small cell lung cancer cells

“…Recent studies have determined that mangiferin protects against liver injury and endothelial dysfunction by inhibiting NLRP3 inflammasome activation in liver and endothelial cells 50,51 . Cao et al reported that mangiferin treatment repressed the expression of NLRP3, the adaptor protein ASC, and caspase‐1, thereby reducing the production of IL‐1β and IL‐18 in mice subject to chronic mild stress 52 . We analyzed the level of NLRP3 in LPS‐induced NSCLC cells and the secretion of IL‐1β in cell supernatants to examine if the anti‐inflammatory mechanism of mangiferin was influenced by NLRP3 inflammasome.…”