title: Madagascine Induces Vasodilatation via Activation of AMPK.
abstract: Madagascine (3-isopentenyloxyemodin) can be chemically synthesized or purified from severalRhamnusspecies, and it is found to have more potent biological activities than the parent compound emodin. The aim of this study is to characterize the vasodilatory effect of madagascine on vasoconstriction and sphingosylphosphorylcholine induced vasospasm inex vivoand reveal the potential mechanismsin vitro. The effects of madagascine on vasoconstriction of rat mesenteric resistance arteries (MRAs) induced by K+, methoxamine, and endothelin-1 were, respectively, studied. The cholesterol-enriched porcine coronary vascular smooth muscle (VSM) strips were used to investigate the effects of madagascine on abnormal constriction induced by sphingosylphosphorylcholine (SPC) which has a pivotal role in vasospasm. The vasodilatory effect was induced by madagascine (0.3-100 μM) in isolated rat MRAs and the vasodilatory effect was blocked by NO synthase inhibitor L-NAME and AMPK inhibitor compound C. Madagascine (10 μM) also significantly relaxed the abnormal constriction in porcine VSM induced by SPC and the effect was abolished by compound C. Madagascine significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in endothelial cells while decreasing the phosphorylation of myosin phosphatase target subunit 1 (MYPT1) in VSM cells. Madagascine-induced vasodilatation was abrogated using small interfering RNA knockdown of AMPK. In summary, madagascine exerted vasodilatation through activating AMPK, leading to the activation of eNOS in endothelium and inhibition of ROCK/MYPT1 in VSM. This study suggests the potential value of madagascine in amelioration of vasospasm related cardiovascular diseases.
authors.affiliation: Dalian Medical University, Dalian China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Chen
authors.affiliation: Yamaguchi University School of Medicine, Yamaguchi Japan.
authors.forename: Bochao
authors.initials: B
authors.lastname: Lv
authors.affiliation: Yamaguchi University School of Medicine, Yamaguchi Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Central Laboratory, the First Affiliated Hospital, Dalian Medical University Dalian, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Dalian Medical University, Dalian China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Sun
authors.affiliation: Dalian Medical University, Dalian China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. D'Annunzio" Chieti-Pescara, Chieti Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Genovese
authors.affiliation: Dipartimento di Farmacia, Università degli Studi "G. D'Annunzio" Chieti-Pescara, Chieti Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Epifano
authors.affiliation: Dalian Medical University, Dalian China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Hou
authors.affiliation: Dalian Medical University, Dalian China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Tang
authors.affiliation: Dalian Medical University, Dalian China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Dalian Medical University, Dalian China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yu
keywords: AMPK; eNOS; madagascine; vasoconstriction; vasospasm