~ 187 ~  Journal of Pharmacognosy and Phytochemistry 2016; 5(2): 187-194 E-ISSN: 2278-4136 P-ISSN: 2349-8234 JPP 2016; 5(2): 187-194 Received: 23-01-2016 Accepted: 25-02-2016 Prashant Kumar Dhakad Assistant Professor, Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Plot No.2, Sector-17A, Yamuna Expressway, Greater Noida, Gautam Budh Nagar, Uttar Pradesh, India. Dr. Pramod Kumar Sharma Dean, School of Medical and Allied Sciences, Galgotias University, Plot No.2, Sector- 17A, Yamuna Expressway, Greater Noida, Gautam Budh Nagar, Uttar Pradesh, India. Dr. Sokindra Kumar Principal, R.V. Northland Institute (RVNI), Greater Noida Dr. Nitin Kumar Director, The Oxford College of Pharmacy, Ghaziabad. Dr. Rupesh Dudhe Assistant Professor, Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Plot No.2, Sector-17A, Yamuna Expressway, Greater Noida, Gautam Budh Nagar, Uttar Pradesh, India. Raghav Mishra Assistant Professor, Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Plot No.2, Sector-17A, Yamuna Expressway, Greater Noida, Gautam Budh Nagar, Uttar Pradesh, India. Correspondence Prashant Kumar Dhakad Assistant Professor, Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Plot No.2, Sector-17A, Yamuna Expressway, Greater Noida, Gautam Budh Nagar, Uttar Pradesh, India. Therapeutic role of phytoconstituents in treatment of cerebral ischemia/reperfusion injury Prashant Kumar Dhakad, Pramod Kumar Sharma, Sokindra Kumar, Nitin Kumar, Rupesh Dudhe, Raghav Mishra Abstract Stroke is important cause of mortality and morbidity in the world. Prevention and effective treatment of stroke is of utmost importance. Stroke involves reduce blood supply in brain to fulfill metabolic demand. Limit in number of medicines and their conventional target approach of action in treating stroke, led us to the search for novel therapeutic approaches. Higher extent of research in field of drug discovery focus on the possible ability of natural compounds extracted from medicinal plants, to prevent ischemia. Natural compounds are promising in treating stroke involving cell process like oxidative phosphorylation, membrane functioning, neurotransmitter release, and free radical generation. Herbal compounds show preventive effect in following sequence - calcium antagonism, anti-excitotoxicity, anti-oxidation, anti- apoptosis and anti-inflammation on experimental induced ischemic brain injury. In this review, we discussed cascade pathway of stroke, role medicinal compounds and novel medical pathway and hypothesis protecting brain ischemia or delay the neurological disorders following a stroke. Keywords: stroke, anti-oxidation, anti-apoptosis, anti-excitotoxicity, anti-inflammation Introduction Stroke is a condition of lacking blood supply to the brain to meet needed energy demand which subjects brain to hypoxia and results to death of neurons or stroke. WHO characterizes stroke as rapidly progressing focal or global disturbance affecting brain roles, and symptoms lasts more than 24 h [1] . Recent survey suggests stroke as third largest cause of mortality after cancer and coronary heart disease and second largest cause of path physiological injury in adults [2] . The case of stroke is 1 per 1000 people [3] although; this incidence varies with age and sex. Arteriovascular diseases is one of the leading causes of death in developed countries [4] leading to neurorehabilitation [5] . Several in-vitro and in-vivo models of brain ischemia reported over the years. The in-vitro models include cultured neurons with or without synaptic formation, glia and cultured brain slice that could only suggest the cytotoxicity of the therapy. The in-vivo animal model of stroke reproduce the etiology, anatomical, and metabolic results of human pathology and allow the study of anti-ischemic drugs clinically proving therapeutic actions [6] . Animal models for stroke meant for screening of drugs classify in three subgroups as global ischemia, focal ischemia and forebrain ischemia (Table 1). Transient or permanent decrease of cerebral blood flow by thromboembolic or thromboembolic occlusion of artery focuses on thrombolytic therapy and is main rational therapeutic strategy for ischemic brain injury [7] . Reperfusion after thrombolytic therapy results in a series of cellular, biochemical and metabolic changes including intracellular reactive oxygen species (ROS) generation, calcium overload, excitotoxic cell injury and inflammation and finally contributes to irreversible brain injury. Tissue plasminogen activator preferred in treating early phase of cerebral ischemia [8] . Cascade pathway of cerebral ischemia Various cell changes weaken the energetic actions that preserve ion gradients [9, 10] . Because of vascular occlusion brain tissue deprives of glucose and oxygen causing build-up of acidic by- products in cell [11, 12] . Decrease in glucose and pH level, lead to end of the electron transport chain within mitochondria causing sharp downfall of ATP and thus failure of energy homeostasis occurs [13, 14] . Deprivation of ATP causes disruption of ionic pump systems like Na + -K + -ATPase, Ca 2+ -H + ATPase, Na + -Ca 2+ transporter resulting in intracellular increase of Na + , Ca 2+ , Cl - concentration and efflux of K + [15, 16] . Redistribution of ions across plasma membrane causes neuronal depolarization, resulting in excess release of neurotransmitters, especially glutamate that causes neuronal excitotoxicity [17, 18] .