Brazilian Green Propolis Suppresses the Hypoxia-Induced Neuroinflammatory Responses by Inhibiting NF-kappa B Activation in Microglia

Hypoxia has been recently proposed as a neuroinflammatogen, which drives microglia to produce proinflammatory cytokines, including interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6. Considering the fact that propolis has hepatoprotective, antitumor, antioxidative, and anti-inflammatory effects, propolis may have protective effects against the hypoxia-induced neuroinflammatory responses. In this study, propolis (50 mu g/mL) was found to significantly inhibit the hypoxia-induced cytotoxicity and the release of proinflammatory cytokines, including IL-1 beta, TNF-alpha, and IL-6, by MG6 microglia following hypoxic exposure (1% O-2, 24 h). Furthermore, propolis significantly inhibited the hypoxia-induced generation of reactive oxygen species (ROS) from mitochondria and the activation of nuclear factor-kappa B (NF-kappa B) in microglia. Moreover, systemic treatment with propolis (8.33 mg/kg, 2 times/day, i.p.) for 7 days significantly suppressed the microglial expression of IL-1 beta, TNF-alpha, IL-6, and 8-oxo-deoxyguanosine, a biomarker for oxidative damaged DNA, in the somatosensory cortex of mice subjected to hypoxia exposure (10% O-2, 4 h). These observations indicate that propolis suppresses the hypoxia-induced neuroinflammatory responses through inhibition of the NF-kappa B activation in microglia. Furthermore, increased generation of ROS from the mitochondria is responsible for the NF-kappa B activation. Therefore, propolis may be beneficial in preventing hypoxia-induced neuroinflammation.