title: One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke.
abstract: 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&amp;#039;s therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multitarget 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 bloodbrain- 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&amp;#039; studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy.
authors.forename: Han-Sen
authors.initials: HS
authors.lastname: Chen
authors.forename: Su-Hua
authors.initials: SH
authors.lastname: Qi
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
authors.forename: Jian-Gang
authors.initials: JG
authors.lastname: Shen
mesh_terms: D000818:Animals; D001205:Ascorbic Acid; D001688:Biological Products / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications; D004359:Drug Therapy, Combination; D005419:Flavonoids; D006801:Humans; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001688:Biological Products; D005419:Flavonoids; C432564:green tea bioflavonoid, zinc ascorbate-containing toothpaste; D010959:Tissue Plasminogen Activator; D001205:Ascorbic Acid