Quassin exerts anti-neuroinflammatory and antidepressant effects through upregulation of A20-mediated modulation of microglia polarization.

Depression is strongly associated with microglia-mediated neuroinflammation, with various studies reporting that modulating the polarization state of microglia is an effective strategy to inhibit neuroinflammation. Quassin, a natural triterpenoid found in the bark of the Quassin amara, has been reported to possess several pharmacological activities. However, its anti-neuroinflammatory and antidepressant effects remain unknown. In this study, a lipopolysaccharide (LPS)-stimulated mouse model was used to examine the anti-neuroinflammatory and antidepressant effects of quassin, and the effect of quassin on microglia was additionally examined in an LPS-induced BV2 model. Further, a PC12 cell model stimulated by BV2 cells in conditioned medium was also established to verify the protective effect of quassin against neuroinflammation-induced neuronal injury. The results of behavioral tests revealed that quassin can inhibit the depressive behaviors of mice. We additionally found that quassin upregulated the expression of A20 and inhibited activation of the NF-κB pathway, further inhibited the M1 microglial markers, and increased the M2 microglial markers. Other investigations concluded that quassin promoted the assembly of the A20 complex and suppressed TRAF6. Finally, this study demonstrated for the first time that quassin exerted anti-neuroinflammatory and antidepressant effects through the upregulation of A20-mediated modulation of microglia polarization. To our knowledge, this study is the first to demonstrate that quassin has potential application value in treating neuroinflammatory-related diseases, especially depression.