6-Gingerol exerts antidepressant effect through regulating the PPARγ signaling pathway

There exists a complex and bidirectional relationship between chronic inflammation and the onset as well as progression of depression. 6-Gingerol, a major bioactive constituent of ginger, possesses notable anti-inflammatory properties. However, its potential therapeutic role in depression and the underlying mechanisms remain insufficiently understood. In this study, we utilized a mouse model of depression induced by chronic unpredictable mild stress (CUMS) to systematically assess the effects of 6-gingerol on depressive-like behaviors and to comprehensively investigate its influence on the phenotype and function of hippocampal microglia. Our findings clearly demonstrate that 6-gingerol significantly alleviates depressive-like behaviors in CUMS-exposed mice in a dose-dependent manner and markedly attenuates microglia-mediated neuroinflammation. Moreover, in vitro experiments confirmed that 6-gingerol regulates microglial polarization through the PPARγ signaling pathway, which may represent a key mechanism underlying its antidepressant activity. Taken together, our results indicate that 6-gingerol exerts antidepressant effects via modulation of the PPARγ pathway, thereby providing a promising therapeutic strategy for the treatment of depression.