Gastroprotective activity of synthetic coumarins: Role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors.
Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20mg/kg. Among the coumarins synthetized, compounds 6 and 10 showed the greatest gastroprotective activity being as active as lansoprazole at 20mg/kg and reducing gastric lesions by 75 and 76%, respectively. Then, in a second experiment, compounds 6 and 10 were re-evaluated in order to understand the possible mode of gastroprotective activity. Regarding coumarin 6, the protective effect was reduced by pre-treatment of the mice with N-ethylmaleimide and l-NAME suggesting that sulfhydryl compounds and endogenous nitric oxide are involved in its gastroprotective activity. While for coumarin 10 the effect was reduced by pre-treatment with indomethacin suggesting that prostaglandins are positively involved in its gastroprotective activity.
Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Quillota 980, Viña del Mar, Chile.
Beatriz
B
Sepulveda
Facultad de Ciencias de la Salud, Instituto de Etnofarmacología (IDEA), Universidad Arturo Prat. Casilla 121, Iquique, Chile.
Cristina
C
Quispe
Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Casilla 567, Valdivia 5090000, Chile.
Mario
M
Simirgiotis
Facultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Carrera 22 Calle 67, Ibagué, Colombia.
Alfredo
A
Torres-Benítez
Facultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Carrera 22 Calle 67, Ibagué, Colombia.
Johanna
J
Reyes-Ortíz
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. Electronic address: areche@uchile.cl.
Carlos
C
Areche
Facultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Carrera 22 Calle 67, Ibagué, Colombia. Electronic address: jose.garcia@unibague.edu.co.
Olimpo
O
García-Beltrán
D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D003374:Coumarins; D011453:Prostaglandins; D013438:Sulfhydryl Compounds; D050916:TRPV Cation Channels; D009569:Nitric Oxide
Coumarins; Gastroprotective; Heterocycles; Ulcer