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Gastroprotective effect of a flavone from Lonchocarpus araripensis Benth. (Leguminosae) and the possible mechanism.
J Pharm Pharmacol. 2008 Mar; 60(3):391-7.JP

Abstract

The gastroprotective effect of DDF (3,6-dimethoxy-6'', 6''-dimethyl-[2'', 3'' : 7,8]-chromeneflavone) from Lonchocarpus araripensis Benth. (Leguminosae) on gastric damage induced by absolute ethanol (96%, 0.2 mL/mouse) and indometacin (30 mg kg(-1), p.o.) in mice was investigated. Intraperitoneally administered DDF at dose levels of 50, 100 and 200 mg kg(-1) markedly reduced the gastric lesions in the ethanol model by 62, 72 and 96%, and in the indometacin model by 34, 70 and 75%, respectively, as compared with misoprostol (50 microg kg(-1), p.o.), the reference compound that caused lesion suppression by 67% in ethanol model and by 72% against indometacin-induced ulceration. The ED50 of DDF in reducing gastric lesions induced by ethanol and indometacin (dose of the DDF that reduced the gastric lesion area by 50% in relation to the control value) was 50.87 and 61.56 mg kg(-1), respectively. Mechanistic studies were carried out at 100 mg kg(-1) DDF using the ethanol model. Compared with N-acetylcysteine (750 mg kg(-1), p.o.), a donor of sulfhydryls, DDF only partially replenished the ethanol-induced depletion of gastric mucosal NP-SH. Pretreatment with TRPV1 antagonist capsazepine (5 mg kg(-1), i.p.) or the non-selective cyclooxygenase inhibitor indometacin (10 mg kg(-1), p.o.) effectively blocked the gastroprotective effect of DDF (100 mg kg(-1)) against ethanol damage. Furthermore, the effect of DDF was significantly reduced in mice pretreated with L-NAME, or glibenclamide, the respective inhibitors of nitric oxide synthase and K+ ATP channel activation. These data provide evidence to show that DDF affords gastroprotection against gastric damage induced by ethanol and indometacin by different and complementary mechanisms, which include involvement of endogenous prostaglandins, nitric oxide release, the activation of TRPV1 receptor or K+ ATP channels, besides a sparing effect on NP-SH reserve.

Authors+Show Affiliations

Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Caixa Postal 3157, 60430-270, Fortaleza, Ceará, Brasil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18284821

Citation

Campos, Deive A., et al. "Gastroprotective Effect of a Flavone From Lonchocarpus Araripensis Benth. (Leguminosae) and the Possible Mechanism." The Journal of Pharmacy and Pharmacology, vol. 60, no. 3, 2008, pp. 391-7.
Campos DA, de Lima AF, Ribeiro SR, et al. Gastroprotective effect of a flavone from Lonchocarpus araripensis Benth. (Leguminosae) and the possible mechanism. J Pharm Pharmacol. 2008;60(3):391-7.
Campos, D. A., de Lima, A. F., Ribeiro, S. R., Silveira, E. R., Pessoa, O. D., Rao, V. S., & Santos, F. A. (2008). Gastroprotective effect of a flavone from Lonchocarpus araripensis Benth. (Leguminosae) and the possible mechanism. The Journal of Pharmacy and Pharmacology, 60(3), 391-7. https://doi.org/10.1211/jpp.60.3.0016
Campos DA, et al. Gastroprotective Effect of a Flavone From Lonchocarpus Araripensis Benth. (Leguminosae) and the Possible Mechanism. J Pharm Pharmacol. 2008;60(3):391-7. PubMed PMID: 18284821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gastroprotective effect of a flavone from Lonchocarpus araripensis Benth. (Leguminosae) and the possible mechanism. AU - Campos,Deive A, AU - de Lima,Almi F, AU - Ribeiro,Saulo Rodrigo L, AU - Silveira,Edilberto R, AU - Pessoa,Otilia Deusdênia L, AU - Rao,Vietla S, AU - Santos,Flávia A, PY - 2008/2/21/pubmed PY - 2008/4/15/medline PY - 2008/2/21/entrez SP - 391 EP - 7 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 60 IS - 3 N2 - The gastroprotective effect of DDF (3,6-dimethoxy-6'', 6''-dimethyl-[2'', 3'' : 7,8]-chromeneflavone) from Lonchocarpus araripensis Benth. (Leguminosae) on gastric damage induced by absolute ethanol (96%, 0.2 mL/mouse) and indometacin (30 mg kg(-1), p.o.) in mice was investigated. Intraperitoneally administered DDF at dose levels of 50, 100 and 200 mg kg(-1) markedly reduced the gastric lesions in the ethanol model by 62, 72 and 96%, and in the indometacin model by 34, 70 and 75%, respectively, as compared with misoprostol (50 microg kg(-1), p.o.), the reference compound that caused lesion suppression by 67% in ethanol model and by 72% against indometacin-induced ulceration. The ED50 of DDF in reducing gastric lesions induced by ethanol and indometacin (dose of the DDF that reduced the gastric lesion area by 50% in relation to the control value) was 50.87 and 61.56 mg kg(-1), respectively. Mechanistic studies were carried out at 100 mg kg(-1) DDF using the ethanol model. Compared with N-acetylcysteine (750 mg kg(-1), p.o.), a donor of sulfhydryls, DDF only partially replenished the ethanol-induced depletion of gastric mucosal NP-SH. Pretreatment with TRPV1 antagonist capsazepine (5 mg kg(-1), i.p.) or the non-selective cyclooxygenase inhibitor indometacin (10 mg kg(-1), p.o.) effectively blocked the gastroprotective effect of DDF (100 mg kg(-1)) against ethanol damage. Furthermore, the effect of DDF was significantly reduced in mice pretreated with L-NAME, or glibenclamide, the respective inhibitors of nitric oxide synthase and K+ ATP channel activation. These data provide evidence to show that DDF affords gastroprotection against gastric damage induced by ethanol and indometacin by different and complementary mechanisms, which include involvement of endogenous prostaglandins, nitric oxide release, the activation of TRPV1 receptor or K+ ATP channels, besides a sparing effect on NP-SH reserve. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/18284821/Gastroprotective_effect_of_a_flavone_from_Lonchocarpus_araripensis_Benth___Leguminosae__and_the_possible_mechanism_ L2 - https://doi.org/10.1211/jpp.60.3.0016 DB - PRIME DP - Unbound Medicine ER -