Abstract: Objective To investigate the effects of cornel iridoid glycoside (CIG) on the mitochondria damage induced by cerebral ischemia reperfusion injury in middle cerebral artery occlusion (MCAO) rats. Methods Male SD rats were subjected to MCAO surgery and the right artery was occluded for 2 h followed by reperfusion. All rats were randomly divided into 5 groups (n=6):sham group, model group, CIG 60mg/kg group, CIG 120 mg/kg group, and extract of Ginkgo biloba (EGB) group. Drugs were intragastrically administered at 6th hour after reperfusion, once a day for 7 days. Modified Neurological Severity Scores (mNSS) was carried out to evaluate the neurological functioning in MCAO rats. The mitochondrial ultrastructure in injured cortex of MCAO rats was detected by transmission electron microscopy. The expression of mitochondrial function related proteins NIX, Beclin1, DRP1, OPA1, and PGC-1α were evaluated using Western blotting. Results The MCAO rats scored significantly higher in mNSS, and mitochondrial ultrastructure was damaged in injured cortex. Furthermore, the expression of NIX, Beclin1, DRP1, OPA1, and PGC-1α were also remarkably downregulated in the injured cortex of MCAO rats. While treatment with CIG declined the mNSS scores, ameliorated the mitochondrial injury, and significantly increased the expression of NIX, Beclin1, DRP1, OPA1, and PGC-1α in the injured cortex of MCAO rats. Conclusion CIG treatment could increase the mitochondrial biogenesis, fission and fusion process, and activate the mitophagy, hence ameliorate the mitochondrial injury, promote the recovery of neurological function after MCAO injury in rats. Our research showed that CIG may be a candidate drug for cerebral stroke therapy.

Key words: cornel iridoid glycoside, cerebral ischemia reperfusion, neuronal protection, mitochondria injury, mitophagy, mitochondria fission and fusion