Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara.
trans-Dehydrocrotonin (DHC), the major diterpene isolated from Croton cajucara Benth, was assayed for antiulcerogenic activity in four induced gastric ulcer models in the rat. At an oral dose of 100 mg/kg DHC showed a significant antiulcerogenic effect on ulcers induced by hypothermic restraint stress, ethanol, and pylorus ligature. No significant changes in indomethacin-induced gastric lesions or modifications in gastric parameters such as wall mucus, secretion rate, pH, and total acid content were found after DHC treatment. The acute toxicological effects of DHC were assessed in mice. The LD50 values were 876 mg/kg and 47.2 mg/kg for oral and intraperitoneal administrations, respectively. The cytotoxicity of DHC was also studied. A dose-dependent inhibition of cell viability was observed in V-79 fibroblast cell cultures with an IC50 of 240 microM. The high yields of DHC obtained from dried C. cajucara barks as well as its good antiulcerogenic activity and low toxicity support the pharmacological study of this compound as a potential new antiulcerogenic drug.
Brito
A R
AR
Dep. de Fisiologia e Biofísica, Universidade Estadual de Campinas, São Paulo, Brasil. abrito@aleph.com.br
Rodríguez
J A
JA
Hiruma-Lima
C A
CA
Haun
M
M
Nunes
D S
DS
D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002927:Cimetidine / Q000627:therapeutic use; D004224:Diterpenes / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D045785:Diterpenes, Clerodane; D000431:Ethanol; D007213:Indomethacin; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D013315:Stress, Psychological
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D045785:Diterpenes, Clerodane; C103060:dehydrocrotonin; D000431:Ethanol; D002927:Cimetidine; D007213:Indomethacin