AUTHOR=Cai Heng , Huang Lin-Yan , Hong Rui , Song Jin-Xiu , Guo Xin-Jian , Zhou Wei , Hu Zhao-Li , Wang Wan , Wang Yan-Ling , Shen Jian-Gang , Qi Su-Hua 

TITLE=Momordica charantia Exosome-Like Nanoparticles Exert Neuroprotective Effects Against Ischemic Brain Injury via Inhibiting Matrix Metalloproteinase 9 and Activating the AKT/GSK3β Signaling Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.908830

DOI=10.3389/fphar.2022.908830

ISSN=1663-9812

ABSTRACT=The neuroprotective effect of plant exosome-like nanoparticles (ELNs) remains unknown. In the present study, we isolated and characterized a novel ELNs from Momordica charantia (MC) and investigated the neuroprotective effects against cerebral ischemia-reperfusion injury. In the present study, MC-ELNs were isolated by ultracentrifugation and characterized. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and MC-ELNs injection intravenously. The integrity of blood brain barrier (BBB) was examined by Evans blue staining, and with the expression of matrix metalloproteinase 9 (MMP-9), Claudin-5 and ZO-1. Neuronal apoptosis was evaluated by TUNEL and the expression of apoptotic proteins including Bcl2, Bax and cleaved Caspase 3. The major discoveries include that: (1) Dil-labelled MC-ELNs was identified in infarct area; (2) MC-ELNs treatment significantly ameliorated the BBB disruption, decreased infarct sizes, and reduced neurological deficit scores; (3) MC-ELNs treatment obviously down-regulated the expression of MMP-9 and up-regulated the expression of ZO-1 and Claudin-5. Small RNA sequencing revealed that MC-ELNs derived miRNA5266 reduced MMP-9 expression. Furthermore, MC-ELNs treatment significantly up-regulated AKT/GSK3β signaling pathway and attenuated neuronal apoptosis in HT22 cells.  Taken together, these findings indicate that MC-ELNs attenuate ischemia-reperfusion-induced damage to the BBB, and inhibit neuronal apoptosis probably via up-regulation of AKT/GSK3β signaling pathway.