No abstract

The polyphenolic compound resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical which has been found in more than 70 plant species, including herbs and human food products such as grapes, berries, and peanuts. Resveratrol was first isolated in 1940; however, little attention was paid to it until its benefits in coronary heart disease were studied in 1992. Since then, increasing evidence has indicated that resveratrol may be useful in treating cardiovascular diseases, cancers, pain, inflammation, tissue injury, and in reducing the risk of neurodegenerative disorders, especially Alzheimer's disease (AD). AD is characterized by a progressive dementia, and is one of the most common neurodegenerative disorders in the elderly. It has been reported that resveratrol exhibits neuroprotective benefits in animal models of AD. Resveratrol promotes the non-amyloidogenic cleavage of the amyloid precursor protein, enhances clearance of amyloid beta-peptides, and reduces neuronal damage. Despite the effort spent trying to understand the mechanisms by which resveratrol functions, the research work in this field is still incomplete. Many concerns such as bioavailability, biotransformation, synergism with other dietary factors, and risks inherent to its possible pro-oxidant activities still need to be addressed. This review summarizes and discusses the neuroprotective effects of resveratrol on AD, and their potential mechanisms.

Significance: Hydrogen sulfide (H 2 S) has traditionally been considered a toxic environmental pollutant. In the late 1990s, the presumed solely harmful role of H 2 S has been challenged because H 2 S may also be involved in the maintenance and preservation of cardiovascular homeostasis. Recent Advances: The production of endogenous H 2 S has been attributed to three key enzymes, cystathionine c-lyase (CSE), cystathionine b-synthase, and 3-mercaptopyruvate sulfurtransferase. The recognition of H 2 S as the third gaseous signaling molecule has stimulated research on a multitude of pathophysiologic events in the cardiovascular system. In particular, important roles in cardiovascular disorder processes are ascribed to the CSE/H 2 S pathway, such as atherosclerosis, myocardial infarction, hypertension, and shock. Critical Issues: Many biological activities and molecular mechanisms of H 2 S in the cardiovascular system have been demonstrated in studies using different tools, such as the genetic overexpression of CSE, the direct administration of H 2 S donors, or the use of H 2 S-releasing prodrugs. Unfortunately, the role of the CSE/H 2 S pathway in cardiovascular disease remains controversial in numerous areas, and many questions regarding the gaseous molecule still remain unanswered. Future Directions: Advances in basic research indicate that the CSE/H 2 S pathway may provide potential therapeutic targets for treating cardiovascular disorders. But the molecular targets of H 2 S still need to be identified. Antioxid. Redox Signal. 17, 106-118.

BackgroundHydrogen sulfide (H2S), the third physiologically relevant gaseous molecule, is recognized increasingly as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the effects and mechanisms of sodium hydrosulfide (NaHS, a H2S donor) on tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVEC) dysfunction.Methodology and Principal FindingsApplication of NaHS concentration-dependently suppressed TNF-α-induced mRNA and proteins expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), mRNA expression of P-selectin and E-selectin as well as U937 monocytes adhesion to HUVEC. Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1), was induced and coincident with the anti-inflammatory action of NaHS. Furthermore, TNF-α-induced NF-κB activation assessed by IκBα degradation and p65 phosphorylation and nuclear translocation and ROS production were diminished in cells subjected to treatment with NaHS.SignificanceH2S can exert an anti-inflammatory effect in endothelial cells through a mechanism that involves the up-regulation of HO-1.

Phosphodiesterase-5 (PDE5) inhibitors are predominantly used in the treatment of erectile dysfunction, and have been recently shown to have a potential therapeutic effect for the treatment of Alzheimer's disease (AD) through stimulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling by elevating cGMP, which is a secondary messenger involved in processes of neuroplasticity. In the present study, the effects of a PDE5 inhibitor, icarrin (ICA), on learning and memory as well as the pathological features in APP/PS1 transgenic AD mice were investigated. Ten-month-old APP/PS1 transgenic mice overexpressing human amyloid precursor protein (APP695swe) and presenilin 1 (PS1-dE9) were given ICA (30 and 60 mg/kg) or sildenafil (SIL) (2 mg/kg), age-matched wild-type (WT) mice were given ICA (60 mg/kg), and APP/PS1 and WT control groups were given an isovolumic vehicle orally twice a day for four months. Results demonstrated that ICA treatments significantly improved learning and memory of APP/PS1 transgenic mice in Y-maze tasks. The amyloid precursor protein (APP), amyloid-beta (Aβ1-40/42) and PDE5 mRNA and/or protein levels were increased in the hippocampus and cortex of APP/PS1 mice, and ICA treatments decreased these physiopathological changes. Furthermore, ICA-treated mice showed an increased expression of three nitric oxide synthase (NOS) isoforms at both mRNA and protein levels, together with increased NO and cGMP levels in the hippocampus and cortex of mice. These findings demonstrate that ICA improves learning and memory functions in APP/PS1 transgenic mice possibly through the stimulation of NO/cGMP signalling and co-ordinated induction of NOS isoforms.

No abstract

The present study attempts to investigate the effects of S-propargyl-cysteine (SPRC), a sulfur-containing amino acid, on lipopolysaccharide (LPS)-induced inflammatory response in H9c2 cardiac myocytes. We found that SPRC prevented nuclear factor-κB (NF-κB) activation assessed by NF-κB p65 phosphorylation and IκBα degradation, suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and intracellular reactive oxygen species (ROS) production. Furthermore, incubation of H9c2 cells with SPRC induced phosphorylation of Akt in a time- and concentration-dependent manner. In addition, SPRC attenuated LPS-induced mRNA and protein expression of tumor necrosis factor-α (TNF-α), and mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS). The effects of SPRC were abolished by cystathionine γ-lyase [CSE-an enzyme that synthesizes hydrogen sulfide (H(2)S)] inhibitor, DL: -propargylglycine (PAG), SPRC-induced Akt phosphorylation and TNF-α release was also abolished by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Furthermore, SPRC also increased LPS-induced down-regulation expression of CSE and H(2)S level in H9c2 cells. PAG abolished SPRC-induced up-regulation of H(2)S level. Therefore, we concluded that SPRC produced an anti-inflammatory effect in LPS-stimulated H9c2 cells partly through the CSE/H(2)S pathway by impairing IκBα/NF-κB signaling and by activating PI3K/Akt signaling pathway.

No abstract