Open AccessPseudoginsenoside‐F11 attenuates cerebral ischemic injury by alleviating autophagic/lysosomal defects
Author(s) -
Liu YueYang,
Zhang TianYu,
Xue Xue,
Liu DongMei,
Zhang HaoTian,
Yuan LinLin,
Liu YingLu,
Yang HanLin,
Sun ShiBo,
Zhang Cheng,
Xu HeSong,
Wu ChunFu,
Yang JingYu
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12702
Subject(s) - autophagy , neuroprotection , microglia , medicine , ischemia , tunel assay , pharmacology , lysosome , stroke (engine) , apoptosis , chemistry , pathology , inflammation , immunohistochemistry , biochemistry , mechanical engineering , engineering , enzyme
Summary Aims Pseudoginsenoside‐F11 ( PF 11), an ocotillol‐type ginsenoside, has been reported to exert wide‐ranging neuroprotective properties. The aim of this study was to investigate the effect and potential mechanisms of PF 11 on the autophagic/lysosomal pathway following ischemic stroke. Methods Male Sprague‐Dawley rats underwent permanent middle cerebral artery occlusion ( pMCAO ). Cerebral ischemia outcome, TUNEL staining, Fluoro‐Jade B staining were carried out 24 hours poststroke. The autophagic/lysosomal‐related proteins were measured. Results A single administration of PF 11 significantly decreased the infarct area, reduced the brain water content, and improved neurological functions, even 4 hours after the onset of pMCAO . Meanwhile, PF 11 lessened the ischemic insult‐mediated loss of neurons and activation of astrocytes and microglia. Furthermore, PF 11 attenuated pMCAO ‐induced accumulations of autophagosomes and apoptosis. We further observed a remarkable effect of PF 11 in reversing the ischemic insult‐induced accumulation of autophagosomes ( LC 3‐ II ) and abnormal aggregation of autophagic proteins ( SQSTM 1 and ubiquitin). Furthermore, PF 11 was capable of improving lysosomal function and lysosome/autophagosome fusion following pMCAO , and this change was reversed by the lysosomal inhibitor chloroquine. Also, the improvement of ischemic outcome and the antiapoptotic effect induced by PF 11 was reversed by CQ. Conclusion These findings indicate that the autophagic flux is impaired in a rat model of pMCAO , and that PF 11 exerts an excellent protective effect against ischemic stroke by alleviating autophagic/lysosomal defects.