Pathophysiology of ischemic reperfusion injury and the molecular targets involved in amelioration of brain injury by herbal medicine

Introduction and objectives. A number of preclinical evaluations of stroke treatment with herbal medicine (HM) have been reported. The aim of the current review was to highlight the pathophysiology of stroke and review the pre-clinically identified molecular mechanisms of HM treatment. Materials and method. Only 32 articles published in the English language were accessible on Google scholar describing the treatment and mechanistic processes of HM in animal models of stroke, as well as human clinical trials, and were reviewed in this study. Results and discussion. Suboptimal Na+/K+ ATPases pump activity, actions of microglia cytokines that increase the level intracellular adhesion molecules-1 (ICAM-1) which promote WBC extravasation with associated increased in matrix metalloproteinase (MMP) activity (digest basement-membranes), explains edema and apoptosis/inflammation. Altered conductivity in injured neurons with compensatory increase in glutamate release that overwhelms the regulatory glial glutamate transporter 1, and thus peaks the level of glutamate to an excitotoxin leve, promotes neuronal death. Glutamate activity on NMDAR promotes oxidative stress, lipid peroxidation and release/influx of Ca2+ that causes apoptosis. The molecular targets involved in the treatment for stroke by HM promote anti-apoptotic/anti-inflammation, anti-oxidation, angiogenesis, neurogenesis, anticoagulation/fibrinolysis effects and optimal metabolism. Different HM promotes the activities of tissue plasminogen activator, haemeoxygenase 1, Neutrin-1, brain derived neurotropic factor (BDNF) and mitogen-activated protein kinase (MAPK). Conclusion. The pathophysiology of stroke and the preclinical targets on which HM act to ameliorate them were identified which could serve as a focus for research on the development of effective treatment for stroke.