1. Role of Nitric Oxide and Hydrogen Sulfide in the Vasodilator Effect of Ursolic Acid and Uvaol from Black Cherry Prunus serotina Fruits.
- Author
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Luna-Vázquez FJ, Ibarra-Alvarado C, Rojas-Molina A, Romo-Mancillas A, López-Vallejo FH, Solís-Gutiérrez M, Rojas-Molina JI, and Rivero-Cruz F
- Subjects
- Alkynes antagonists & inhibitors, Alkynes pharmacology, Animals, Aorta cytology, Aorta drug effects, Aorta metabolism, Cyclic GMP metabolism, Cystathionine gamma-Lyase chemistry, Cystathionine gamma-Lyase metabolism, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Enzyme Activation drug effects, Fruit chemistry, Glyburide antagonists & inhibitors, Glyburide pharmacology, Glycine analogs & derivatives, Glycine antagonists & inhibitors, Glycine pharmacology, Hydrogen Sulfide metabolism, KATP Channels agonists, KATP Channels metabolism, Male, Molecular Docking Simulation, NG-Nitroarginine Methyl Ester antagonists & inhibitors, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type III chemistry, Nitric Oxide Synthase Type III metabolism, Plant Extracts chemistry, Protein Binding, Rats, Triterpenes isolation & purification, Vasodilator Agents isolation & purification, Ursolic Acid, Hydrogen Sulfide agonists, Nitric Oxide agonists, Prunus avium chemistry, Triterpenes pharmacology, Vasodilation drug effects, Vasodilator Agents pharmacology
- Abstract
The present research aimed to isolate the non-polar secondary metabolites that produce the vasodilator effects induced by the dichloromethane extract of Prunus serotina (P. serotina) fruits and to determine whether the NO/cGMP and the H2S/KATP channel pathways are involved in their mechanism of action. A bioactivity-directed fractionation of the dichloromethane extract of P. serotina fruits led to the isolation of ursolic acid and uvaol as the main non-polar vasodilator compounds. These compounds showed significant relaxant effect on rat aortic rings in an endothelium- and concentration-dependent manner, which was inhibited by NG-nitro-L-arginine methyl ester (L-NAME), DL-propargylglycine (PAG) and glibenclamide (Gli). Additionally, both triterpenes increased NO and H2S production in aortic tissue. Molecular docking studies showed that ursolic acid and uvaol are able to bind to endothelial NOS and CSE with high affinity for residues that form the oligomeric interface of both enzymes. These results suggest that the vasodilator effect produced by ursolic acid and uvaol contained in P. serotina fruits, involves activation of the NO/cGMP and H2S/KATP channel pathways, possibly through direct activation of NOS and CSE.
- Published
- 2016
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