An Angiopep-2 functionalized nanoformulation enhances brain accumulation of tanshinone IIA and exerts neuroprotective effects against ischemic stroke. (2nd October 2018)

• Record Type: Journal Article
• Authors: Li, Yutao; Dang, Yanxin; Han, Dandan; Tan, Yong; Liu, Xin; Zhang, Fengming; Xu, Yuan; Zhang, Haiyan; Yan, Xianfeng; Zhang, Xiaoxu; Zeng, Zhiyong; Sun, Xiaojun
• Is Part Of: New journal of chemistry. Volume 42:Number 21(2018)
• Page Start: 17359
• Page End: 17370
• Publication Date: 2018-10-02
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c8nj02441c
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Effective intervention against ischemic stroke requires delivery of potent neuroprotective drugs to the brain. Abstract : Effective intervention against ischemic stroke requires delivery of potent neuroprotective drugs to the brain. Tanshinone IIA (TSIIA), the major bioactive ingredient extracted from the root of Salvia miltiorrhiza Bunge, is a proven neuroprotective compound, but its therapeutic application is hampered by chemical instability, low solubility, and inability to cross the blood brain barrier (BBB). Herein we report that a nanoformulation with a high-loading of TSIIA functionalized with Angiopep-2 effectively increased its brain accumulation by ∼12 fold, reduced infarct volume in an experimental stroke model by 2 fold, and augmented rat motor function scores after stroke by 60%. We confirm that the anti-ischemic stroke is mediated by inhibition of neuronal apoptosis, depletion of proinflammatory cytokines, and reversal of intracellular calcium [Ca 2+ ]i overload in neurons. Moreover, we reveal for the first time that the underlying molecular mechanism for this formulation of TSIIA involves inhibition of the inflammatory signaling pathway HMGB1/TLRs/MyD88/NF-κB.