Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling.

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.

Green tea is one of the most beverages with antioxidants and nutrients. As one of the major components of green tea, (-)-epicatechin gallate (ECG) was evaluated for its antioxidative properties in the present study. Cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R) to investigate potential anti-ischemia/reperfusion injury properties of ECG in vitro. Markers of oxidative stress as ROS, LDH, MDA, and SOD were further assayed in our study. Data indicated that ECG could affect neovascularization and promote cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy through affecting VEGF, Bcl-2, BAX, LC3B, caspase 3, mTOR, and Beclin-1 expression. All the data suggested that ECG may be protective for the brain against ischemia/reperfusion injury by promoting neovascularization, alleviating apoptosis and autophagy, and promoting cell proliferation in HBMVECs of OGD/R.

This study aimed to investigate whether the routine administration of escitalopram for three months would improve the prognosis of patients with ischemic stroke and decrease the plasma copeptin level. A total of 97 patients with acute cerebral infarction were randomly allocated to receive escitalopram (5-10 mg once per day, orally; n=49) or not to receive escitalopram (control group; n=48) for 12 weeks starting at 2-7 days after the onset of stroke. Both groups received conventional treatments, including physiotherapy and secondary prevention of stroke. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the disability of patients at the initial evaluation and at the monthly follow-up visits for three months. Impairment in the daily activities was assessed using the Barthel Index (BI), while cognitive impairment was assessed using Mini-Mental State Examination (MMSE) score. The psychiatric assessment included the administration of the Present State Examination modified to identify Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms of depression. The severity of depression was measured using the 17-item Hamilton Rating Scale for Depression (HAMD). During the 3month follow-up period, 95 patients were included in the analysis (two patients withdrew from the escitalopram group). NIHSS and BI improvement at the 90th day were significantly greater in the escitalopram group (Po0.05), while HAMD and plasma copeptin levels significantly decreased, compared to the control group (Po0.01). In patients with acute ischemic stroke, the earlier administration of escitalopram for three months may improve neurological functional prognosis and decrease copeptin level.