title: Role of Nitric Oxide and Hydrogen Sulfide in the Vasodilator Effect of Ursolic Acid and Uvaol from Black Cherry Prunus serotina Fruits.
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.
authors.affiliation: Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro 76010, Mexico. fjlunavz@yahoo.com.mx.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Luna-Vázquez
authors.affiliation: Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro 76010, Mexico. cibarra@uaq.mx.
authors.forename: César
authors.initials: C
authors.lastname: Ibarra-Alvarado
authors.affiliation: Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro 76010, Mexico. rojasa@uaq.mx.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Rojas-Molina
authors.affiliation: Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro 76010, Mexico. romtono@comunidad.unam.mx.
authors.forename: Antonio
authors.initials: A
authors.lastname: Romo-Mancillas
authors.affiliation: Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro 76010, Mexico. fabianhlv@gmail.com.
authors.forename: Fabián H
authors.initials: FH
authors.lastname: López-Vallejo
authors.affiliation: Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro 76010, Mexico. mariasolisgutierrez@gmail.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Solís-Gutiérrez
authors.affiliation: Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Querétaro 76010, Mexico. jirojas@gmail.com.
authors.forename: Juana I
authors.initials: JI
authors.lastname: Rojas-Molina
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria s/n, México D.F. 04510, Mexico. joserc@unam.mx.
authors.forename: Fausto
authors.initials: F
authors.lastname: Rivero-Cruz
mesh_terms: D000480:Alkynes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000737:chemistry / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D005905:Glyburide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000819:agonists* / Q000378:metabolism; D054086:KATP Channels / Q000819:agonists / Q000378:metabolism; D008297:Male; D062105:Molecular Docking Simulation; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000819:agonists* / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D011485:Protein Binding; D000068220:Prunus avium / Q000737:chemistry*; D051381:Rats; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000480:Alkynes; D006152:Cyclic GMP; D003542:Cystathionine gamma-Lyase; D005905:Glyburide; D005998:Glycine; D006862:Hydrogen Sulfide; D054086:KATP Channels; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D010936:Plant Extracts; D014315:Triterpenes; D014665:Vasodilator Agents; D000097245:Ursolic Acid; C009055:propargylglycine; C496316:Nos3 protein, rat; C013330:uvaol
keywords: Prunus serotina; hydrogen sulfide; in silico study; nitric oxide; ursolic acid; uvaol; vasodilation