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 Alzheimers 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 γ-lyase (CSE), cystathionine β-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 pro-drugs. 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.

Phosphodiesterase-5 (PDE5) inhibitors are predominantly used in the treatment of erectile dysfunction, and have been recently shown to have a potentia

Inflammation in central nervous system (CNS) plays a vital role in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (DLB), HIV-related dementia and traumatic brain injury. Icariside II (ICS II), an active flavonoid compound derived from a Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to possess a neuroprotective effect on AD model. However, whether ICS II has a directly protective effect on acute neuroinflammation remains still unclear. Therefore, the current study was designed to investigate the possible protective effect of ICS II on acute neuroinflammation induced by intracerebroventricular (ICV) injection of lipopolysaccharide (LPS), and further to explore its possible mechanism. After ICS II was prophylactically administered for 7 days before LPS injection, the rats were randomly divided into five groups as follows: sham group (n = 9), sham + ICS II-H (10 mg/kg) (n = 9), LPS (n = 14), LPS + ICS II-L (3 mg/kg) (n = 14), LPS + ICS II-H (10 mg/kg) (n = 14) groups, respectively. As expected, LPS injection exhibited neuronal morphological damage, and ionized calcium binding adapter molecule 1 (IBA-1) of microglia and glial fibrillary acidic protein (GFAP) of astrocyte were activated. However, pre-treatment with ICS II not only inhibited the activation of microglia and astrocyte, but also significantly reversed the expressions of inflammatory factors such as interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), cyclooxygenase-2 (COX-2), as well as the expressions of Toll-Like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and TNF receptor associated factor 6 (TRAF6). Furthermore, ICS II inhibited the degradation of IκB and the following activation of NF-κB. Hence it is concluded that ICS II attenuates LPS-induced neuroinflammation through inhibiting TLR4/MyD88/NF-κB pathway in rats, and it has potential value as a new therapeutic agent to treat neuroinflammation-related diseases, such as AD.