Emerging evidence suggests that neuroinflammation and oxidative stress may be major contributors to major depressive disorder (MDD). Patients or animal models of depression show significant increase of proinflammatory cytokine interleukin-1β (IL-1β) and oxidative stress biomarkers in the periphery or central nervous system (CNS). Recent studies show that hydrogen selectively reduces cytotoxic oxygen radicals, and hydrogen-rich saline potentially suppresses the production of several proinflammatory mediators. Since current depression medications are accompanied by a wide spectrum of side effects, novel preventative or therapeutic measures with fewer side effects might have a promising future. We investigated the effects of drinking hydrogen-rich water on the depressive-like behavior in mice and its underlying mechanisms. Our study show that hydrogen-rich water treatment prevents chronic unpredictable mild stress (CUMS) induced depressive-like behavior. CUMS induced elevation in IL-1β protein levels in the hippocampus, and the cortex was significantly attenuated after 4 weeks of feeding the mice hydrogen-rich water. Over-expression of caspase-1 (the IL-1β converting enzyme) and excessive reactive oxygen species (ROS) production in the hippocampus and prefrontal cortex (PFC) was successfully suppressed by hydrogen-rich water treatment. Our data suggest that the beneficial effects of hydrogen-rich water on depressive-like behavior may be mediated by suppression of the inflammasome activation resulting in attenuated protein IL-1β and ROS production.

It is known that oxidative stress plays a pivotal role in age-related macular degeneration (AMD) pathogenesis. Alpha-mangostin is the main xanthone purified from mangosteen known as anti-oxidative properties. The aim of the study was to test the protective effect of alpha-mangostin against oxidative stress both in retina of light-damaged mice model and in hydrogen peroxide (H2O2)-stressed RPE cells. We observed that alpha-mangostin significantly inhibited light-induced degeneration of photoreceptors and 200 μM H2O2-induced apoptosis of RPE cells. 200 μM H2O2-induced generation of reactive oxygen species (ROS) and light-induced generation of malondialdehyde (MDA) were suppressed by alpha-mangostin. Alpha-mangostin stimulation resulted in an increase of superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity and glutathione (GSH) content both in vivo and vitro. Furthermore, the mechanism of retinal protection against oxidative stress by alpha-mangostin involves accumulation and the nuclear translocation of the NF-E2-related factor (Nrf2) along with up-regulation the expression of heme oxygenas-1 (HO-1). Meanwhile, alpha-mangostin can activate the expression of PKC-δ and down-regulate the expression of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, P38. The results suggest that alpha-mangostin could be a new approach to suspend the onset and development of AMD.