Dehydroleucodine (DhL), a sesquiterpene lactone (SQL) of the guaianolide ty
pe isolated from Artemisia douglasiana Besser, shows a pharmacological cyto
protective effect and significantly prevents the formation of gastric and d
uodenal lesions induced by various necrotising agents in rodents. The effec
ts of DhL, on two models of experimental colitis were examined. Colitis was
produced in male Wistar rats by rectal instillation of 5 and 10% acetic ac
id, following the methods of Eliakim et al. and Le Duc et al., respectively
. In mice colitis was produced by rectal instillation of 0.1 ml of 2,4,6-tr
initrobenzene sulphonic acid (5 mg in 50% ethanol) (TNB) as previously desc
ribed by Chin et al. In this study, the administration of DhL 40 mg kg(-1)
(1 h before the induction of colitis) significantly decreased mucosal damag
e. This effect was consistent in both models. The protection provided by Dh
L was accompanied by significant decreases in diarrhoea and colon weight; a
nd histologically normal mucosa without ulceration and mucus production wer
e observed. This study shows that both TNB and acetic acid colitis can be p
harmacologically controlled by DhL. Our results suggest that the protective
activity of DhL in experimental colitis is mediated, at least in part, thr
ough the increase of glycoprotein synthesis, anti-inflammatory effect and i
nhibition of COX-2 induction, and by inhibiting the degranulation of cells
containing monoamines. (C) 1999 Academic Press.