Gastroprotective mechanisms of centipedic acid, a natural diterpene from Egletes viscosa LESS.
This study was aimed to clarify the mechanisms of gastroprotection by centipedic acid (CPA), a natural diterpene from Egletes viscosa LESS. (Asteraceae) using ethanol-induced gastric mucosal damage in mice and gastric secretion in 4-h pylorus-ligated rats as model systems. In mice, intragastrically administered CPA (25, 50, 100 mg/kg) greatly reduced the mucosal lesions induced by 96% ethanol (0.2 ml, p.o.) by 18, 53, and 79%, respectively, whereas N-acetylcysteine (NAC, 300 mg/kg, i.p.), the reference compound produced a 50% inhibition. In 4-h pylorus-ligated rats, CPA (50 mg/kg) applied intraduodenally decreased both gastric secretory volume and total acidity. Similar to NAC, the plant diterpene effectively prevented the ethanol associated decrease in non-proteic sulfhydryls (NP-SH) and the elevated thiobarbituric acid-reactive substances (TBARS) in gastric tissue, suggesting that these compounds exert an antioxidant effect. Pretreatment of mice with indomethacin, the cyclooxygenase inhibitor but not with capsazepine, the transient receptor potential vanilloid-1 (TRPV1)-receptor antagonist greatly suppressed the gastroprotective effect of CPA. Furthermore, CPA gastroprotection was significantly attenuated in mice pretreated with L-NAME or glibenclamide the respective inhibitors of nitric oxide synthase and K(+)(ATP) channel activation. These data suggest that CPA affords gastroprotection by different and complementary mechanisms, which include a sparing effect on NP-SH reserve, and roles for endogenous prostaglandins, nitric oxide, and TRPV1-receptor and K(+)(ATP) channel activation.
Guedes
Marjorie Moreira
MM
Department of Physiology and Pharmacology, Post-Graduate Programme in Medical Sciences, Faculty of Medicine, Federal University of Ceará, Brazil.
Carvalho
Ana Carla da Silva
AC
Lima
Alana Fontales
AF
Lira
Silveria Regina de Sousa
SR
de Queiroz
Samia Sousa
SS
Silveira
Edilberto Rocha
ER
Santos
Flávia Almeida
FA
Rao
Vietla Satyanarayana
VS
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000897:Anti-Ulcer Agents; D019659:Asteraceae / Q000737:chemistry*; D002211:Capsaicin / Q000494:pharmacology; D002492:Central Nervous System Depressants; D004224:Diterpenes / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000473:pathology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011708:Pylorus / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D002492:Central Nervous System Depressants; D004224:Diterpenes; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D016166:Free Radical Scavengers; D005663:Furans; D007004:Hypoglycemic Agents; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C531023:centipedic acid; D000431:Ethanol; D002211:Capsaicin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine; D007213:Indomethacin