Gastroprotective effect of barbatusin and 3-beta-hydroxy-3-deoxibarbatusin, quinonoid diterpenes isolated from Plectranthus grandis, in ethanol-induced gastric lesions in mice.
BACKGROUND
Validate the popular use of Plectranthus grandis in gastric disorders through the active components.


OBJECTIVE
Isolation of barbatusin (BB) and 3beta-hydroxy-3-deoxibarbatusin (BBOH), diterpenes from Plectranthus grandis, and evaluation of their gastroprotective effect and possible mechanisms of action.


METHODS
Isolation and chemical characterization of diterpenes from Plectranthus grandis by chromatographic and spectroscopic methods and evaluation of gastroprotective action of the diterpenes through ethanol-induced gastric injury in mice model. It was evaluated the effect of capsazepine, indomethacin and the role of nitric oxide and K(ATP-) channels on the gastroprotective effect of BBOH and BB. Additionally it was measured the concentrations of gastric mucus, non-proteic-sulfhydryl groups and total thiobarbituric acid-reactive substances.


RESULTS
Orally administered BBOH and BB at doses of 5 and 10mg/kg, markedly reduced the gastric lesions by 59 and 96%, and 32 and 76%, respectively, with superior results as compared to N-acetylcysteine (150 mg/kg, i.p.), reference compound that caused 85% lesion suppression. Although BBOH presented a higher gastroprotection than BB they act by similar mechanisms in relation to N-acetylcysteine, and prevent the depletion of gastric mucus, gastric mucosal non-proteic-sulfhydryl groups as well as the increase in thiobarbituric acid-reactive species. Moreover, the gastroprotective effect of BB was effectively blocked in mice pretreated with TRPV1 antagonist capsazepine, by the non-selective cyclooxygenase inhibitor indomethacin, or by the nitric oxide synthase inhibitor L-NAME but not by K(+)(ATP) channel inhibitor glibenclamide. In contrast, the gastroprotective effect of BBOH was blocked only by indomethacin and glibenclamide pretreatments.


CONCLUSIONS
The protective role for BBOH and BB affording gastroprotection against gastric damage induced by ethanol indicates that these compounds contribute for the activity of Plectranthus species. The different modes of action are probably related to differences in their chemical structure.
Rodrigues
Patrícia de Araújo
Pde A
State University of Ceará, Post-Graduate Programme of Veterinary Sciences, Veterinary Faculty, Fortaleza, CE, Brazil.
de Morais
Selene Maia
SM
de Souza
Carolina Melo
CM
Silva
Ana Raquel Araújo
AR
de Andrade
Geanne Matos
GM
Silva
Maria Goretti Vasconcelos
MG
Albuquerque
Roberto Lima
RL
Rao
Vietla Satyanarayana
VS
Santos
Flávia Almeida
FA
D000111:Acetylcysteine; D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009093:Mucus / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D031346:Plectranthus / Q000737:chemistry*; D011809:Quinones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism
C551252:3-hydroxy-3-deoxibarbatusin; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D004224:Diterpenes; D010936:Plant Extracts; D011809:Quinones; D013438:Sulfhydryl Compounds; D013858:Thiobarbiturates; C551251:barbatusin; D000431:Ethanol; C071423:capsazepine; C029684:thiobarbituric acid; D002211:Capsaicin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine; D007213:Indomethacin