Better understanding the neuroprotective mechanisms of Korean ginseng in stroke

Abstract

Ginseng (Panax ginseng) has many protective effects that include treatment of disabilities caused by traumatic brain injury, stroke, multi-infarct dementia, cerebral arteriosclerosis, cerebral edema, inflammation, Alzheimer's disease and vascular dementia related to age . Although many of its reported actions have been attributed to their antioxidant properties, the cellular mechanisms involved in these effects remain unclear. Recently, Nrf2 has been described as a key regulator of inflammation and oxidative balance. These studies suggest that the major role of Nrf2 is to protect cells from oxidative damage by inducing the expression of several genes of cytoprotective proteins. The enzyme heme oxygenase ( HO ) is one of these targets, which appears to play a protective role in oxidative stress, inflammation and ischemia. The HO cleaves heme (a pro- oxidant) to form biliverdin / bilirubin (which are antioxidants). Considering that under normal conditions the HO exerts a neuroprotective activity, drugs that increase the expression of HO1, its inducible form, would have a potentially beneficial effect. Since the potential of ginseng as a preventive medicine is, at least in part, due to its antioxidant and anti-inflammatory effects; and that the transcription factor Nrf2 and HO enzyme also play various roles in oxidative stress and inflammation, we develop the hypothesis that perhaps the Nrf2 and HO1 could participate of the neuroprotective effects of ginseng. To evaluate this hypothesis, mice will be pre-treated with ginseng extract in different experimental conditions and subjected to a model of focal ischemia. Physiological and behavioral parameters, such as weight, temperature, motor coordination, etc, will be assessed before and after ischemia protocol on different days. At the end the animals will be sacrificed by deep anesthesia and perfused for removal of brain tissue, which will be subjected to histological analysis to quantify the extent of injury and degree of protection obtained with treatment. Some brain slices will be used for evaluation of proteins of interest as Nrf2 and HO1 by immunohistochemistry. Other assays can be done using inhibitors of protein synthesis or specific blockers of certain cellular pathways to better understanding of the ginseng's mechanisms of action, when appropriate. The dose and duration of treatment will be adjusted continuously searching to determine the therapeutic window and lowest effective dose. The post-ischemia treatment also will be evaluated, similar to that reported for the pre-treatment. Depending on the results, studies with aged mice may also be performed. (AU)