Natural trans-crotonin: the antiulcerogenic effect of another diterpene isolated from the bark of Croton cajucara Benth.
The nor-clerodane diterpene trans-crotonin isolated from the bark of Croton cajucara BENTH. was investigated for its ability to prevent the formation of gastric-mucosa ulceration in different experimental models in mice. The results obtained from crotonin were compared with those obtained with another diterpene, DHC (trans-dehydrocrotonin) in the same models. When previously administered (p.o.) at the dose of 100 mg/kg, crotonin, as well as DHC, significantly reduced (p<0.05) gastric injury induced by stress (72, 67%), indomethacin/bethanechol (78, 29%) and pylorus ligature (35, 30%). In the HCl/ethanol-induced gastric ulcer model, at oral doses of 100 and 250 mg/kg, crotonin significantly prevented (p<0.05) the formation of gastric lesions by 51 and 56%, respectively, when compared to the control group. Gastric injury was also of significantly less magnitude in the DHC treatment group (p<0.05). In the pylorus-ligature model, crotonin (p.o.), like cimetidine, increased the volume of gastric juice when compared to the control group (p<0.05). No significant modifications where found in gastric parameters such as pH or total acid content after oral crotonin treatment. However, systemic alterations were observed when crotonin (100 mg/kg) was previously administered intraduodenally to mice. We observed significant changes (p<0.001) in gastric-juice parameters such as an increase in volume and a decrease in gastric acidity. Those pre-treated with crotonin as well as with DHC did not increase free mucus production (p>0.05). The results suggest that crotonin presents a significant anti-ulcer effect when assessed in these ulcer-induced models. As with DHC, the antiulcerogenic effects of crotonin are probably related to anti-secretory or/and gastroprotective properties of this substance. In light of results obtained with DHC and natural trans-crotonin in the present study, we concluded that the A-ring of both diterpenes is not directly involved in the antiulcerogenic activity.
Hiruma-Lima
Clélia Akiko
CA
Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil. hiruma@ibb.unesp.br
Toma
Walber
W
Gracioso
Juliano de Souza
Jde S
de Almeida
Ana Beatriz Albino
AB
Batista
Leĵnia Maria
LM
Magri
Luciana
L
de Paula
Ana Cláudia Bensuaski
AC
Soares
Femanda Rocha
FR
Nunes
Domingos Sávio
DS
Souza Brito
Alba Regina Monteiro
AR
D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D029802:Croton / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D045785:Diterpenes, Clerodane; D008297:Male; D051379:Mice; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000188:drug therapy
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D010936:Plant Extracts; C103060:dehydrocrotonin; C403585:trans-crotonin