Effect of berberine against cerebral ischemia and reperfusion involving in the methylation of PPARγ promoter

Cerebral ischemia has higher incidence and causes irreversible damage to people. As a traditional drug for anti-inflammation, berberine (BBR) has recently been reported to have protective effect against cerebral ischemia. However, the mechanism has not been explored thoroughly. By employing in vivo and in vitro models for cerebral ischemia and reperfusion, we studied the mechanism of BBR against the ischemia-reperfusion. We found that BBR regulated the expression of peroxisome proliferator-activated receptor (PPARγ) in a specific way upon ischemia-reperfusion injury. BBR enhanced the PPARγ expression during cerebral ischemia-reperfusion. By inhibiting PPARγ activity uisng GW9662, a PPARγ inhibitor, we confirmed that BBR protected the mouse brain against the ischemia in a PPARγ-dependent mechanism. In addition, we found that BBR reduced the overall global methylation, declined the expressions of DNMT1 (DNA methyltransferases 1) and DNMT3a (DNA methyltransferases 3a) in the ischemia-reperfusion and reduced the methylation of PPARγ promoter region. Therefore, our data suggested that PPARγ was one of major targets of BBR, and such BBR-induced PPARγ expression during cerebral ischemia and reperfusion might be correlated to the reduced methylation of PPARγ promoter.