Protective effect of hexane extracts of Uncaria sinensis against photothrombotic ischemic injury in mice

Ethnopharmacological relevanceUncaria sinensis (US) has been used in traditional Korean medicine to treat vascular disease and to relieve various neurological symptoms.Aim of the studyScientific evidence related to the effectiveness or action mechanism of US on cerebrovascular disease has not been examined experimentally. Here, we investigated the cerebrovascular protective effect of US extracts on photothrombotic ischemic injury in mice.Materials and methodsUS hexane extracts (HEUS), ethyl acetate extracts (EAEUS) and methanol extracts (MEUS) were administered intraperitoneally 30 min before ischemic insults. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, neurological score and the activation of Akt and eNOS in ischemic brain.ResultsHEUS more significantly reduced infarct volume and edema than did EAEUS and MEUS following photothrombotic cortical occlusion. HEUS produced decreased infarct volume and edema size, and improved neurological function in a concentration-dependent manner (10, 50, and 100 mg/kg). However, HEUS did not reduce brain infarction in eNOS KO mice, suggesting that the protective effect of HEUS is primarily endothelium-dependent. Furthermore, HEUS (10-300 μg/ml) produced a concentration-dependent relaxation in mouse aorta and rat basilar artery, which was not seen in eNOS KO mouse aorta, suggesting that HEUS cause vasodilation via an eNOS-dependent mechanism. This correlated with increased phosphorylation of Akt and eNOS in the brains of HEUS-treated mice.ConclusionHEUS prevent cerebral ischemic damage by regulating Akt/eNOS signaling. US, herbal medicine, may be the basis of a novel strategy for the therapy of stroke.