Natural trans-Crotonin: The Antiulcerogenic Effect of Another Diterpene Isolated from the Bark of Croton cajucara Benth.

Abstract

Croton cajucara BENTH. (Euphorbiaceae), commonly known as "sacaca," is widely used as an aromatic and bitter tea made from the bark and leaves of a plant in Amazonian folk medicine for the treatment of a wide range of gastrointestinal symptoms. 1,2) We also reported the antiulcerogenic activity of DHC (trans-dehydrocrotonin), the principal furano diterpene isolated from C. cajucara bark, on indomethacin-, hypothermic restraint-stress-, ethanol-and pylorus ligature-induced gastric ulcers in mice and rats.3) We also studied possible antiulcerogenic mechanisms involved in the action of DHC.4) The acute and subchronic toxicity of this compound was also studied by our group through both in vivo and in vitro assays showing oral toxicity when administered for a short period of time (35 d).3,5) Besides DHC, we also studied the antiulcerogenic activity of other diterpenes with a clerodane skeleton such as cordatin and aparisthman with excellent results. 6,7)We describe here the isolation of the second most important nor-clerodane diterpene from the bark of this plant, crotonin, and our study of its antiulcerogenic activity on indomethacin/bethanechol-, hypothermic restraint-stress-and pylorus ligature-induced gastric ulcer in mice. In the HCl/ethanol model, we studied whether the effect of crotonin was dose-dependent compared with that of cimetidine. The parameters of gastric-acid secretion such as gastric acidity and gastric-juice volume were analyzed in animals submitted to the Shay method and treated with crotonin by the oral and intraduodenal route. Moreover, the effects of crotonin on free mucus production were also determined. Data for DHC was also included for comparison in all experiments. Regarding the structure activity relationship, by comparing the antiulcerogenic activity of DHC and crotonin, we can evaluate the importance of parts of both molecules for the bioactivity tested.

Cytoprotective Effect of UlGen, a Polyherbal Formulation against Physical and Chemical Factor Induced Gastric Ulcers in Wister Albino Rats

“…The alkaloid fraction and both alkaloids demonstrated potent antiulcerogenic effects when evaluated in gastric lesioninduced animals, Simaba ferruginea St. Hill (Simaroubaceae) [24] . Phytochemical investigation on hydroethanolic extract of the leaves (HEL) and bark (HEB) from the plant Alchornea castaneaefolia and enriched flavonoidic fraction led to the isolation of flavonoids glycosides as the main compounds, thus suggesting that these substances may be involved in the observed antiulcer activity [12] . The severity of the reaction of ulcerogen and the reduction of ulcer size by SNE was evident by histological findings.…”

Uma revisão das atividades biológicas da trans-desidrocrotonina, um produto natural obtido de Croton cajucara

“…A atividade antiulcerogênica foi também comprovada, para o 19-nor-clerodano trans-crotonina, que difere da DCTN apenas pela ausência da insaturação Δ 3,4 do anel A do sistema decalínico, bem como para o óleo fi xo das cascas do caule do Croton cajucara (Almeida et al, 2003;Hiruma-Lima et al, 2000;Hiruma-Lima et al, 2002). Como os clerodados CTN, cis-cajuarina B e transcajuarina B foram evidenciados em baixos percentuais, neste óleo, (Souza et al, 2006) deve existir uma ação conjunta destes clerodanos para o efeito gastroprotetor deste óleo.…”

“…Dentre estes derivados, a CTN e os clerodanos-butenolídeos CJCR e ICJCR se destacam por serem de ocorrência natural, tendo sido isolados como constituintes minoritários das cascas do caule do Croton cajucara (Maciel et al, 1998a,b). Desta forma, a semi-síntese destes componentes permitiu a realização de testes biológicos; a CTN-derivado por exemplo, provou ser um agente antiulcerogênico efi caz (Maciel et al, 2000;Melo et al, 2004;Hiruma-Lima et al, 2002). No entanto, a perda da insaturação Δ 3,4 (CTN-natural ou derivado, por comparação com a DCTN) reduziu a atividade antitumoral da molécula em testes in vivo em tumores ascíticos, e in vitro em linhagens de células tumorais ascíticas (Grynberg et al, 1999).…”

“…No entanto, ambos os clerodanos DCTN [carbonila (C2) α,β-insaturada (Δ 3,4 )] e CTN (carbonila-C2) apresentaram efeito antiulcerogênico. Neste caso, é provável que o anel A do sistema decalínico destes clerodanos, não esteja diretamente envolvido na sua atividade antiulcerogênica, estando portanto, a subunidade lactona (Maciel et al, 2000;Hiruma-Lima et al, 2002).…”

Comparative anti-inflammatory and antinociceptive effects of terpenoids and an aqueous extract obtained from Croton cajucara Benth

“…The biological importance of natural and semisynthetic CTN has been reported (Grynberg et al, 1999;Maciel et al, 2000;Hiruma-Lima et al, 2002;Almeida et al, 2002;Anazetti et al, 2003). Regarding to AAA biological importance, this compound proved to possess antibiotic (Addae-Mensah et al, 1992) and antibacterial (Peres et al, 1997) activities.…”