An Angiopep-2 functionalized nanoformulation enhances brain accumulation of tanshinone IIA and exerts neuroprotective effects against ischemic stroke
作者： Yutao Li , Yanxin Dang , Dandan Han , Yong Tan , Xin Liu
DOI: 10.1039/C8NJ02441C
关键词: Pharmacology 、 HMGB1 、 Signal transduction 、 Calcium in biology 、 Salvia miltiorrhiza 、 Neuroprotection 、 Proinflammatory cytokine 、 Blood–brain barrier 、 Chemistry 、 Stroke
摘要: Effective intervention against ischemic stroke requires delivery of potent neuroprotective drugs to the brain. Tanshinone IIA (TSIIA), major bioactive ingredient extracted from root Salvia miltiorrhiza Bunge, is a proven compound, but its therapeutic application hampered by chemical instability, low solubility, and inability cross blood brain barrier (BBB). Herein we report that nanoformulation with high-loading TSIIA functionalized Angiopep-2 effectively increased accumulation ∼12 fold, reduced infarct volume in an experimental model 2 augmented rat motor function scores after 60%. We confirm anti-ischemic mediated inhibition neuronal apoptosis, depletion proinflammatory cytokines, reversal intracellular calcium [Ca2+]i overload neurons. Moreover, reveal for first time underlying molecular mechanism this formulation involves inflammatory signaling pathway HMGB1/TLRs/MyD88/NF-κB.
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