Cerebral ischemia-reperfusion (CI/R) injury remains a major medical problem due to the lack of effective
therapies. Previous studies have shown that increasing the activity of the
transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and gene targets in cell culture and
stroke animal models is highly neuroprotective.
Oxymatrine is the major
quinolizidine alkaloid extracted from the root of Sophora flavescens AIT, and has been proved to be protective after
ischemia in recent studies. The present study was designed to investigate the potential effect of
oxymatrine in
ischemia-reperfusion injury in rat's brain and to explore the possible role of
oxymatrine in Nrf2 pathway. The results indicated that the ischemic
infarct and
edema were significantly reduced in rats that received
oxymatrine, with a corresponding improvement in neurological function after CI/R. In immunohistochemistry and Western blotting analyses, Nrf2 and hemeoxygenase-1 (HO-1) were up-regulated in ischemic cortex, beginning at 6 h, peaking at 48 h and declining at 72 h after CI/R.
Intraperitoneal injection of
oxymatrine inhibited the production of lipid peroxidation and increased the activities of Nrf2 and HO-1 in rats brain after CI/R. Taken together, these results suggest that
oxymatrine administered systemically protected brain against focal
ischemia-
reperfusion damage at the early stage of
stroke, and that activating Nrf2/HO-1 pathway may contribute to the neuroprotective action of
oxymatrine in rat focal
brain ischemia-reperfusion model. Thus, treatment of
stroke with
oxymatrine may prevent severe consequences after brain attack.