期刊
CURRENT NEUROPHARMACOLOGY
卷 15, 期 1, 页码 134-156出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570159X14666160620102055
关键词
Combination therapy; hemorrhagic transformation; ischemic stroke; multi-target; natural compounds; neurotoxicity; tissue plasminogen activator (t-PA)
资金
- Hong Kong General Research Fund (GRF) [17102915, 776512M]
- Research Grant Council, Hong Kong SAR
- National Natural Science Foundation of China [31270902, 81171075]
- Seed Funding Programme for Basic Research, University of Hong Kong [201411159208]
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [13KJA310005]
Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro-and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy.
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