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1.
Naunyn Schmiedebergs Arch Pharmacol ; 394(3): 437-446, 2021 03.
Article in English | MEDLINE | ID: mdl-33034715

ABSTRACT

Arterial hypertension is a risk factor for various cardiovascular and renal diseases, representing a major public health challenge. Although a wide range of treatment options are available for blood pressure control, many hypertensive individuals remain with uncontrolled hypertension. Thus, the search for new substances with antihypertensive potential becomes necessary. Coumarins, a group of polyphenolic compounds derived from plants, have attracted intense interest due to their diverse pharmacological properties, like potent antihypertensive activities. Braylin (6-methoxyseselin) is a coumarin identified in the Zanthoxylum tingoassuiba species, described as a phosphodiesterase-4 (PDE4) inhibitor. Although different coumarin compounds have been described as potent antihypertensive agents, the activity of braylin on the cardiovascular system has yet to be investigated. To investigate the vasorelaxation properties of braylin and its possible mechanisms of action, we performed in vitro studies using superior mesenteric arteries and the iliac arteries isolated from rats. In this study, we demonstrated, for the first time, that braylin induces potent vasorelaxation, involving distinct mechanisms from two different arteries, isolated from rats. A possible inhibition of phosphodiesterase, altering the cyclic adenosine monophosphate (cAMP)/cAMP-dependent protein kinase (PKA) pathway, may be correlated with the biological action of braylin in the mesenteric vessel, while in the iliac artery, the biological action of braylin may be correlated with increase of cyclic guanosine monophosphate (cGMP), followed by BKCa, Kir, and Kv channel activation. Together, these results provide evidence that braylin can represent a potential therapeutic use in preventing and treating cardiovascular diseases.


Subject(s)
Coumarins/pharmacology , Iliac Artery/drug effects , Mesenteric Arteries/drug effects , Vasodilator Agents/pharmacology , Animals , Iliac Artery/physiology , Male , Mesenteric Arteries/physiology , Potassium Channels/physiology , Rats, Wistar , Vasodilation/drug effects
2.
Braz J Biol ; 70(2): 443-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20549071

ABSTRACT

Molecular plant components have long been aimed at the angiogenesis and anti-angiogenesis pathways, and have been tested as sources for antineoplasic drugs with promising success. The present work deals with the anti-angiogenic effects of Methyl Jasmonate. Jasmonate derivatives were demonstrated to selectively damage the mitochondria of cancer cells. In vitro, 1-10 mM Methyl Jasmonate induced the cell death of the human umbilical vein endothelial cells (HUVEC) and the Murine melanoma cells (B16F10), while micromolar concentrations were ineffective. In vivo, comparable concentrations were toxic and reduced the vessel density of the Chorioallantoic Membrane of the Chicken Embryo (CAM). However, 1-10 microM concentrations produced a complex effect. There was increased capillary budding, but the new vessels were leakier and less organised than corresponding controls. It is suggested that not only direct toxicity, but also the drug effects upon angiogenesis are relevant to the antineoplasic effects of Methyl Jasmonate.


Subject(s)
Acetates/pharmacology , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents/pharmacology , Chorioallantoic Membrane/drug effects , Cyclopentanes/pharmacology , Endothelial Cells/drug effects , Oxylipins/pharmacology , Animals , Cell Line, Tumor , Chick Embryo , Chorioallantoic Membrane/blood supply , Endothelial Cells/cytology , Humans , Umbilical Veins/cytology , Umbilical Veins/drug effects
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