Investigation of anti-inflammatory and antinociceptive activities of trans-dehydrocrotonin, a 19-nor-clerodane diterpene from Croton cajucara .1.

The anti-inflammatory and antinociceptive effects of trans-dehydrocrotonin, isolated from the bark of Croton cajucara (Euphorbiaceae), were investigated using several animal models. The trans-dehydrocrotonin produced a significant inhibition of carrageenin-induced paw edema and cotton pellet granuloma in rats. It also inhibited the writhings in mice induced by acetic acid, but did not show a significant effect in the hot-plate test in mice. The LD(50) of t-DCTN was 555.0 mg/kg (p.o.) for mice

Ethnopharmacology, phytochemistry and pharmacology: a successful combination in the study of Croton cajucara

Phytochemical and pharmacological studies of Croton cajucara were oriented by traditional medicine. the stem bark of the mature plant is a rich source of clerodane-type diterpenes: trans-dehydrocrotonin (DCTN), trans-crotonin (CTN), cis-cajucarin B, cajucarin A, cajucarinolide and two novel clerodanes, trans-cajucarin B and sacacarin. in young (18-month-old) plants, the triterpene acetyl aleuritolic acid (AAA) was the major stem bark component and in these the diterpene DCTN was not present. the highest concentration of DCTN (1.4% of dry bark) was detected in 4-6 year-old plants, while 3-year-old plants contained only 0.26% of this diterpene. Three steroids (p-sitosterol, stigmasterol and sitosterol-3-O-beta-glucoside), two flavonoids (kaempferol 3,4',7-trimethyl ether and 3,7-dimethyl ether) and one diterpene (cajucarinolide) were isolated from the leaves of this Croton. the main pharmacological activity was correlated with DCTN. This clerodane produced anti-inflammatory and antinociceptive effects and a significant hypoglycemia in alloxan-induced diabetic rats. the compound also reduced the index of gastric lesions induced by restraint-in-cold. Dose-related DCTN and CTN inhibited in vivo the basal acid secretion in pylorus-ligature rats and oxyntic glands isolated from rabbit gastric mucosa, DCTN, CTN or AAA decreased in vitro uptake basal acid secretion induced by histamine and measured with the C-14-aminopyrine uptake method. Uniquely DCTN inhibited C-14-AP uptake induced by bethanechol. the terpenoids, DCTN and AAA, and the chloroform extract of 6-month-old plants reduced gastrointestinal transit in mice. the effects of DCTN and CTN on the survival of mice bearing Sarcoma 180 and Ehrlich carcinoma ascitic tumors, on the proliferation of cultured cells and TNF alpha were determined. DCTN was also evaluated for a possible antioestrogenic activity using the immature rat as a model system for bioassay of oestrogen and for an anti-implantation effect in regularly cycling rats. the biological experiments, using the plant extracts and the terpenoids DCTN, CTN and AAA, are herein discussed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.Univ Fed Rio de Janeiro, Inst Quim, BR-21945970 Rio de Janeiro, BrazilUFPA, CCEN, Dept Quim, Belem, Para, BrazilUniv Fed Rural Rio de Janeiro, IB, Dept Ciencias Fisiol, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, EPM, Dept Farmacol, Setor Prod Nat, São Paulo, BrazilUniv Fed Rural Rio de Janeiro, Dept Quim, Rio de Janeiro, BrazilUniv Estadual Londrina, CCB, Dept Biol Geral, Londrina, PR, BrazilUniv Fed Ceara, Dept Fisiol & Farmacol, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, EPM, Dept Farmacol, Setor Prod Nat, São Paulo, BrazilWeb of Scienc