一个单体多个靶点:中药单体联用t-PA治疗中风

2017年我们在国际杂志Current neuroppharmacology发表了一篇综述文章,概述了在缺血性中风治疗中,延迟使用溶栓剂rt-PA引出出血转换的细胞分子机制,以及目前中药单体治疗中风的靶点。title:

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

文章中罗列了23个能够同时作用于多个靶点的中药单体,并对靶点进行了分析归纳总结,并对这些单体和t-PA联用的可能性进行分析。最后,我们提出了在中药单体研究以及中药单体和t-PA联用的研究中需要注意的事项,包括药物使用剂量,药物作用时间窗;药物长期效果评价;评价指标;以及药物相互作用等。

23个单体包括:和厚朴酚 (Honokiol);;)(Huperzine A;石杉碱甲- A)(Tanshinone IIA,丹参酮IIA)baicalin(:黄芩苷

葛根素 Puerarin;仙茅 Curculigoside  ;紫草素 Shikonin; 甘草酸 Glycyrrhizin  ;天麻素 Gastrodin;人参皂苷Rg1  Ginsenoside Rg1  ;丹皮酚 Paeonol ;夹竹桃麻素 Apocynin  ;黃芪甲苷IV   Astragaloside IV; 蛇床子素 Osthole ;咖啡酸Caffeic acid;厚朴酚 Magnolol; 粉防己碱 Tetrandrine; 芍药苷 Paeoniflorin; 灯盏花素 Scutellarin ;水飞蓟素Silymarin ;小檗碱 Berberine; 阿魏酸 Ferulic acid; 川芎嗪 Tetramethylpyrazine

作用靶点包括;;Reactive Nitrogen Species (RNS) and Reactive Oxygen Species (ROS);Activated Protein C (APC);N-methyl-D-aspartic Receptor (NMDAR);Platelet-derived Growth Factor-CC (PDGF-CC);Vascular Endothelial Growth Factor (VEGF);High Mobility Group Box Protein 1 (HMGB1);Matrix metalloproteinase-9 (MMP-9); NF-κB:Low-density Lipoprotein Receptor-related Protein 1 (LRP-1)

英文摘要:

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

molecularbioactivitiessimultaneously targeting several importantcurrently available literature with theneurotoxicityin ischemic brain injury. Based on these targets, we select 23 promising compounds fromcurrent progress about molecular targets involving in t-PA-mediated HT and)-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 summarizeneuro- and blood-brain-barrier (BBBneurotoxicity. 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 bothtransformation (HT) and

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.

Keywords: Combination therapy, hemorrhagic transformation, ischemic stroke, multi-target, natural compounds,neurotoxicity, tissue plasminogen activator (t-PA).

文献:

Chen H-S, Qi S-H, Shen J-G. One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke.Current Neuropharmacology. 2017;15(1):134-156.:10.2174/1570159X14666160620102055.doi


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