Abstract
Stroke is a complex neurodegenerative disorder with a clinically high prevalence and mortality. Despite many efforts to protect against ischemic stroke, its incidence and related permanent disabilities continue to increase. In this study, we found that pretreatment with phlorofucofuroeckol (PFF), isolated from brown algae species, significantly increased cell viability in glutamate-stimulated PC12 cells. Additionally, glutamate-stimulated cells showed irregular morphology, but PFF pretreatment resulted in improved cell morphology, which resembled that in cells cultured under normal conditions. We further showed that PFF pretreatment effectively inhibited glutamate-induced apoptotic cell death in a caspase-dependent manner. Reactive oxygen species (ROS) induced by oxidative stress are closely associated with ischemia-induced neurological diseases. Exposure of PC12 cells to glutamate induced abundant production of intracellular ROS and mitochondrial dysfunction, which was attenuated by PFF in a dose-dependent manner. In vivo studies revealed that PFF-mediated prevention was achieved predominantly through inhibition of apoptosis and mitochondrial ROS generation. Taken together, these results suggest the possibility of PFF as a neuroprotective agent in ischemic stroke.
Highlights
Ischemic stroke, the most common type of stroke, is among the leading causes of long-term disability and mortality [1, 2]
Thrombolytic are the only treatment approved by the Food and Drug Administration (FDA), they are useful in only limited situations due to the short time requirement for administration and the high risks for later treatment [5]
Ischemia/reperfusion has been reported to be closely associated with various disorders, including stroke, myocardial infarction, hypovolemic shock, and peripheral vascular disease [36, 37]
Summary
The most common type of stroke, is among the leading causes of long-term disability and mortality [1, 2]. The dramatic disruption of the bloodstream that occurs for minutes in ischemic stroke leads to deficiencies in essential nutrients because of thrombosis or embolism [3]. According to World Health Organization (WHO) statistics, the global stroke burden has increased significantly over the last 20 years, and about 15 million people suffer a stroke each year [4]. Thrombolytic are the only treatment approved by the Food and Drug Administration (FDA), they are useful in only limited situations due to the short time requirement for administration and the high risks for later treatment [5]. The discovery and development of novel neuroprotective drugs for ischemic stroke is important
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