Diosmin protects against cerebral ischemia/reperfusion injury through activating JAK2/STAT3 signal pathway in mice

Abstract

Background and objectApoptosis is a major form of cell death in cerebral ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment. Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic effect in the treatment of varicose veins and renal injury. However, the effect of DM in the acute phase of cerebral I/R is not clear. This study investigated DM’s role in cerebral I/R and its potential mechanism. MethodsMale CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO). Experiment 1 was used to evaluate the time course expression of Janus tyrosine kinase-2 (JAK2), signal transducer and activator of transcription-3 (STAT3), phosphorylated JAK2 (pJAK2) and phosphorylated STAT3 (pSTAT3) after cerebral I/R, and six time points were included. In experiment 2, DM was given orally at doses of 50mg/kg or 100mg/kg for 6 consecutive days before receiving tMCAO. At 24h after reperfusion, neurological deficit, Nissl staining, brain water content and infarct volume were examined. Bcl-2, Bax, pJAK2, and pSTAT3 were detected by immunohistochemistry, qRT-PCR and Western blot. Confocal microscope was used to observe the location of pSTAT3 in the cerebral cortex. ResultsCompared with Vehicle group, the high dose of DM significantly alleviated neurological deficit, brain water content, infarct volume, increased the Nissl-positive cells, upregulated the expression of pJAK2, pSTAT3 and Bcl-2 and downregulated Bax (P<0.05). ConclusionThese results showed that DM protected against cerebral I/R injury through activating JAK2/STAT3 signal pathway.