Neuroprotective effect and mechanism of Mu-Xiang-You-Fang on cerebral ischemia-reperfusion injury in rats

Abstract

Ethnopharmacological relevance: The present study is to investigate the neuroprotective effect of Mu-Xiang-You-Fang (MXYF), a classic Traditional Chinese Medicine used by Chinese minorities to treat stroke, on cerebral ischemia-reperfusion (I/R) injury and the related signaling pathways.

Materials and methods: Male Sprague-Dawley rats were divided into 6 groups: sham group, I/R group, nimodipine and MXYF (58, 116 and 232mg/kg respectively) groups. Cerebral ischemia model was induced by middle cerebral artery occlusion for 2h followed by reperfusion for 48h. Neurological functional score was evaluated according to the method of Zea longa's score and the infarct area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 48h after reperfusion. The protein expression of cytochrome c (cyt-c), Bcl-2, Bax, caspase-9, caspase-3 and caspase-7 were analyzed by western blot and the mRNA expression of Caspase-9, Caspase-3 and Caspase-7 were determined by the reverse transcription-polymerase chain reaction.

Results: Oral administration of MXYF (116 and 232mg/kg) significantly reduced the neurological functional score and attenuated the cerebral infarct area. Western blot analysis showed that the expression of Bcl-2 is enhanced and Bax expression is inhibited after treatment with MXYF (116 and 232mg/kg), leading to significant increase of the ratio between Bcl-2 and Bax. Furthermore, the protein expression of cyt-c, caspase-9, caspase-3 and caspase-7 was significantly inhibited while the mRNA expression of caspase-9, caspase-3 and caspase-7 but not cyt-c was markedly inhibited in the MXYF (116 and 232mg/kg) treatment groups compared with the I/R group.

Conclusions: The above data suggested that MXYF has potential neuroprotective activities by the regulation of apoptotic pathway, MXYF is a promising agent in treatment of stroke.

Keywords: Apoptotic pathway; Caryophyllene (PubChem CID:5281515); Cerebral-ischemia reperfusion injury; Costunolide (PubChem CID:5281437); Dehydrocostus lactone (PubChem CID:73174); Methyl arachidonate (PubChem CID:6421258); Methyleugenol (PubChem CID:7127); Mu-Xiang-You-Fang; Myristicin (PubChem CID:4276); Piperine (PubChem CID:638024); SDS (PubChem CID:3423265); Sesamin(PubChem CID:72303); Tris base (PubChem CID:6503).