Paeonia lactiflora Extract Attenuating Cerebral Ischemia and Arterial Intimal Hyperplasia Is Mediated by Paeoniflorin via Modulation of VSMC Migration and Ras/MEK/ERK Signaling Pathway

Paeonia lactiflora is a well-known traditional Chinese medicine. Paeoniflorin is an active component found in Paeonia lactiflora, which is used to treat smooth muscle spasms and pain and to protect the cardiovascular system. The objective of this study was to determine if Paeonia lactiflora would be protective in rodent models of cerebral ischemia and arterial intimal hyperplasia. Paeonia lactiflora extract (PLex) and paeoniflorin (PF) significantly attenuated cerebral infarction in ischemia/reperfusion injury rats and the severity of intimal hyperplasia in mice where the carotid artery was ligated. PLex and PF reduced PDGF-stimulated VSMC proliferation and migration in a dose-dependent manner by MTT, wound healing, and transwell assays. PF significantly reduced protein levels of Ras, MEK, p-MEK and p-ERK, but not MMP-2 and MMP-9. In summary, Paeonia lactiflora reduced cerebral ischemia and arterial intimal hyperplasia which were mainly made via the intermediary of PF. The protective effect of PF was related to the modulation of the Ras/MEK/ERK signaling pathway.