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Behav Brain Res. 2016 Jan 1;296:318-325. doi: 10.1016/j.bbr.2015.09.031. Epub 2015 Sep 28.

Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain.

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Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
Discipline of Chinese and Western Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, PR China. Electronic address:
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:


Increasing evidence suggests that inflammation and oxidative stress may contribute to the development of major depressive disorder (MDD). Apigenin, a type of bioflavonoid widely found in citrus fruits, has a number of biological actions including anti-inflammatory and antioxidant effects. Although apigenin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study aims to investigate the effects of apigenin on behavioral changes and inflammatory responses induced by chronic unpredictable mild stress (CUMS) in rats. GW9662, a selective peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor, was administered 30 min before apigenin. We found that treatment with apigenin (20mg/kg, intragastrically) for three weeks remarkably ameliorated CUMS-induced behavioral abnormalities, such as decreased locomotor activity and reduced sucrose consumption. In response to oxidative stress, the NLRP3 inflammasome was activated and IL-1β secretion increased in the prefrontal cortex (PFC) of CUMS rats. However, apigenin treatment upregulated PPARγ expression and downregulated the expression of NLRP3, which subsequently downregulated the production of IL-1β. In addition, GW9662 diminished the inhibitory effects of apigenin on the NLRP3 inflammasome. In conclusion, our results demonstrate that apigenin exhibits antidepressant-like effects in CUMS rats, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression via the up-regulation of PPARγ expression.


Apigenin; Chronic unpredictable mild stress; Depression; NLRP3 inflammasome; Peroxisome proliferator-activated receptor-γ

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