Vasorelaxant activity of some structurally related triterpenic acids from Phoradendron reichenbachianum (Viscaceae) mainly by NO production: ex vivo and in silico studies.
The aim of the current study was to investigate the vasorelaxant activity of five structurally-related triterpenic acids namely ursolic (1), moronic (2), morolic (3), betulinic (4) and 3,4-seco-olean-18-ene-3,28-dioic (5) acids. The vasorelaxant effect of compounds 1-5 were determined on endothelium-denuded and endothelium-intact rat aortic rings pre-contracted with noradrenaline (0.1 μM). All compounds showed significant relaxant effect on endothelium-intact vessels in a concentration-dependent manner (p<0.05). Ursolic, moronic and betulinic acids were the most potent vasorelaxant agents with 11.7, 16.11 and 58.46 μM, respectively. Since vasorelaxation was blocked by L-NAME, while indomethacin did not inhibit the effect, endothelium-derived nitric oxide seems to be involved in triterpenic 2 and 3 mode of action. Compounds 1-5 were docked with a crystal structure of eNOS. Triterpenes 1-5 showed calculated affinity with eNOS in the C1 and C2 binding pockets, near the catalytic site; Ser248 and Asp480 are the residues that make hydrogen bonds with the triterpene compounds.
Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico.
Maria Yolanda
MY
Rios
Sugey
S
López-Martínez
Fabian
F
López-Vallejo
José L
JL
Medina-Franco
Rafael
R
Villalobos-Molina
Maximiliano
M
Ibarra-Barajas
Gabriel
G
Navarrete-Vazquez
Sergio
S
Hidalgo-Figueroa
Oswaldo
O
Hernández-Abreu
Samuel
S
Estrada-Soto
D000818:Animals; D001011:Aorta; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006860:Hydrogen Bonding; D007213:Indomethacin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D028184:Phoradendron / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
D010936:Plant Extracts; D014315:Triterpenes; D014665:Vasodilator Agents; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin