Total Flavones of Rhododendron simsii Planch Flower Protect against Cerebral Ischemia-Reperfusion Injury via the Mechanism of Cystathionine-γ-Lyase-Produced H(2)S

Total flavones of Rhododendron simsii Planch flower (TFR) have a significant protective effect against cerebral ischemia-reperfusion injury. However, its mechanism is unclear. This study investigated the protection of TFR against cerebral ischemia-reperfusion injury via cystathionine-γ-lyase- (CSE-) produced H(2)S mechanism. CSE(−/−) mice and CSE-siRNA-transfected rat were used. Relaxation of cerebral basilar artery (CBA), H(2)S, and CSE mRNA were measured. TFR significantly inhibited cerebral ischemia-reperfusion-induced abnormal neurological symptom and cerebral infarct in the normal rats and the CSE(+/+) mice, but not in the CSE(−/−) mice, and the inhibition was markedly attenuated in CSE-siRNA-transfected rat; TFR elicited a significant vasorelaxation in rat CBA, and the relaxation was markedly attenuated by removal of endothelium or CSE-siRNA transfection or coapplication of NO synthase inhibitor L-NAME and PGI(2) synthase inhibitor Indo. CSE inhibitor PPG drastically inhibited TFR-evoked vasodilatation resistant to L-NAME and Indo in endothelium-intact rat CBA. TFR significantly increased CSE mRNA expression in rat CBA endothelial cells and H(2)S production in rat endothelium-intact CBA. The increase of H(2)S production resistant to L-NAME and Indo was abolished by PPG. Our data indicate that TFR has a protective effect against the cerebral ischemia-reperfusion injury via CSE-produced H(2)S and endothelial NO and/or PGI(2) to relax the cerebral artery.