title: Scutellarin Reduces Endothelium Dysfunction through the PKG-I Pathway.
abstract: Purpose. In this report, we investigated the protective mechanism of scutellarin (SCU) in vitro and in vivo which could be involved in endothelial cGMP-dependent protein kinase (PKG), vasodilator stimulated phosphoprotein (VASP) pathway, and vascular endothelium dysfunction (EtD). Method. Human brain microvascular endothelial cells (HBMECs) with hypoxia reoxygenation (HR) treatment and rats with cerebral ischemia reperfusion (CIR) treatment were applied. Protein and mRNA expression of PKG, VASP, and p-VASP were evaluated by Western blot and RT-PCR methods. Vascular EtD was assessed by using wire myography to determine endothelium-dependent vasorelaxation in isolated rat basilar artery (BA). Result. In cultured HBMECs, SCU (0.1, 1, and 10 μM) increased cell viability, mRNA, protein level, and phosphorylative activity of PKG and VASP against HR injury. In HR model of BA, SCU increased protein level of P-VASP. In rat CIR model, wire myography demonstrated that SCU (45 and 90 mg/kg, i.v.) significantly reduced ischemic size by partially restoring the endothelium dependent vasodilation of BA; PKG inhibitor Rp-8-Br-cGMPS (50 μg/kg, i.v.) reversed this protection of SCU in CIR rats. Conclusion. SCU protects against cerebral vascular EtD through endothelial PKG pathway activation.
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China ; Department of Respiratory Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Du
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Pharmacy Department, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Cai
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Na
authors.initials: N
authors.lastname: Hu
authors.affiliation: Pharmacy Department, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
authors.forename: Congji
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacy, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Yang