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 clerodan es, trans-cajucarin B and sacacarin. In young (18-month-old) plants, the tr iterpene acetyl aleuritolic acid (AAA) was the major stem bark component an d 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-sitost erol, stigmasterol and sitosterol-3-O-beta-glucoside), two flavonoids (kaem pferol 3,4',7-trimethyl ether and 3,7-dimethyl ether) and one diterpene (ca jucarinolide) were isolated from the leaves of this Croton. The main pharma cological activity was correlated with DCTN. This clerodane produced anti-i nflammatory and antinociceptive effects and a significant hypoglycemia in a lloxan-induced diabetic rats. The compound also reduced the index of gastri c lesions induced by restraint-in-cold. Dose-related DCTN and CTN inhibited in vivo the basal acid secretion in pylorus-ligature rats and oxyntic glan ds isolated from rabbit gastric mucosa, DCTN, CTN or AAA decreased in vitro uptake basal acid secretion induced by histamine and measured with the C-1 4-aminopyrine uptake method. Uniquely DCTN inhibited C-14-AP uptake induced by bethanechol. The terpenoids, DCTN and AAA, and the chloroform extract o f 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 car cinoma ascitic tumors, on the proliferation of cultured cells and TNF alpha were determined. DCTN was also evaluated for a possible antioestrogenic ac tivity using the immature rat as a model system for bioassay of oestrogen a nd for an anti-implantation effect in regularly cycling rats. The biologica l experiments, using the plant extracts and the terpenoids DCTN, CTN and AA A, are herein discussed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.