Seminars

1) Ischemic stroke is the most common cause of stroke, and it constitutes 80% of the cases that are caused from two main sources, thrombus and embolus. Nowadays, tissue plasminogen activator (tPA), a thrombolytic agent, is used to treat ischemic stroke in order to restore cerebral blood flow which would promote production of large amounts of reactive oxygen species (ROS), mainly from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or NOX, a family of transmembrane proteins. Overproduction of ROS induces oxidative stress, which then activates the nuclear factor kappa-beta (NF-ĸB) signaling pathway to synthesize pro-inflammatory cytokines such as nitric oxide (NO), the tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) which promotes neuronal inflammation, and matrix metalloproteinases-9 (MMP-9) which contribute to the breakdown of extracellular matrix and direct degrading of tight junction (TJ) proteins, leading, thus, to blood brain barrier (BBB) damage. Therefore, removing free radicals or preventing their formation can be a potential therapeutic strategy.

We investigated the effect of dihydrocapsaicin (DHC) on cerebral and blood brain barrier (BBB) damage in cerebral ischemia and reperfusion (I/R) models.

DHC significantly reduced the area of infarction, morphology changes in the neuronal cells including apoptotic cell death, and also decreased the BBB damage. DHC also activated nuclear-related factor-2 (Nrf2) and significantly decreased oxidative stress and inflammation via down-regulated reactive oxygen species (ROS), NADPH oxidase (NOX2, NOX4), nuclear factor kappa-beta (NF-ĸB), and nitric oxide (NO), including matrix metalloproteinases-9 (MMP-9) levels. DHC protected the cerebral and the BBB from I/R injury via attenuation of oxidative stress and inflammation. Therefore, this study offers to aid future development for protection against cerebral I/R injury in humans.

2) Obesity is a risk factor for the development of diabetes and atherosclerosis that recently was linked to incident cardiovascular disease (CVD). Especially, atherosclerosis is a main risk factor for CVD involving the flow of blood. In the vascular vessels, the endothelium is necessary for homeostasis due to the uncontrolled endothelial cell response is involved in many diseases, such as atherosclerosis, hypertension, which are linked to endothelial injury, dysfunction and activation. Obesity is associated with abnormal endothelial function. This often inferred that the reduction in endothelial function is the result of a decrease in nitric oxide (NO). Endothelial dysfunction is recognized as the initial step in the vascular disease and considered as the key early stage of atherosclerosis development. Therefore, we have investigated natural products that beneficial effects of anti-atherosclerotic drugs.

Capsaicinoid nonivamide and rosuvastatin has been shown to exert for anti-inflammation, anti-oxidants and anti-obesity effects in various animal models. We investigated nonivamide (PAVA), rosuvastatin (RSV) and their combination in an obesity-related endothelial dysfunction model. Male Sprague-Dawley rats were given a high-fat diet (HFD rats) and normal chow (ND rats). Interesting, in HFD rats, the combination therapy had a significantly higher effects than the monotherapy on all metabolic parameters; it also improved insulin sensitivity, aorta functional, decreased blood pressure, oxidative stress and prevented vascular damage. The synergistic effect of PAVA and RSV could be alternative treatment against obesity-related complications in patients with cardiovascular disease.