Effects of oroxylin A in cerebral vascular tone regulation (841.3)

Abstract

Oroxylin A, a flavonoid and an active component isolated from Scutellariae baicalensis, has been considered beneficial in preventing inflammation‐induced microglia‐mediated neurodegeneration. Its role in regulation of cerebral vascular smooth muscle tone and blood flow, however, remains unclear. This study was designed to assess possible beneficial effects of oroxylin A in cerebral blood flow and cerebral vascular smooth muscle tone regulation in vitro and in vivo. The results indicated that oroxylin A (10 mg/Kg, iv), which did not affect the systemic blood pressure, significantly increased regional cerebral blood flow in the striatum of the rat in vivo, using laser Doppler flowmetry. Results from tissue bath myography studies indicated that oroxylin A (100 nM ‐ 30 μM) in a concentration‐dependent manner relaxed U46619‐precontracted porcine isolated basilar arteries. The vasorelaxation was not affected by denudation of the endothelium, cold storage for 5 days, tetrodotoxin (0.3 μM), ODQ (10 μM, a soluble guanylate cyclase inhibitor), SQ22536 (200 μM, an adenylate cyclase inhibitor) and H89 (10 μM, an inhibitor of protein kinase A), but was blocked by iberiotoxin (100 nM). These results suggest that oroxylin A induces dilation of large pial arteries and intraparenchymal vessels. The relaxation in large basilar arteries is independent of the endothelium and is mediated by large‐conductance Ca2+‐activated K+ channels on the smooth muscle cells. The vasodilatory effect with increased regional cerebral blood flow of oroxylin A may provide additional benefits in preventing inflammation‐mediated neurodegeneration.