Aspectos farmacológicos das novas norcucurbitacinas glicosídicas de wilbrandia (cf) verticillata

Abstract

The purified fraction of the rhizome of Wilbrandia (cf) vertiçillata (cabeça de negro) that contained two novel norcucurbitacin glucosides and identified as Wv^ and WV2 was investigated for its possible anti-inflammatory, an tifertility, laxative and cytotoxic cffects. In mice, the LD^g values for the fraction by ip and oral routes wcre 345 1 11 and 975 1 99 mg/kg respecti vely while in KB cell lines, it demonstrated low cytotoxicity with an ED^g of 12 pg/ml. In rat models of inflammation, the fraction demonstrated significant (p < 0,05) anti-inflammatory activity. The carrageenan-induced paw edema was inhibited by 25,4 and 39,5% at doses of 100 and 200 mg/1<g respectively. At 100 mg/kg, carrageenan-induced granulomatous lesion was inhibited by 45,82% where as the formaldehyde-induced arth ritis was supressed on the tenth dav of observation by 63,42%. Besides, the capillary permeability induced by acetic acid in mice was effectively reduced in a dose depen dent manner. The reduction was 69,11 and 90,36% for the rejs pective doses of 50 and 100 mg/kg po. The fraction at an oral dose of 50mg/kg exhibited laxative property by promoting wet. faeces and its effect was comparable to 0,5 mg/kg of Isocucurbitacin B. xx xx i At 100 mg/kg po, the fraction prolonged the dies trus phase of the reproductive cycle in mice but this effect was however, found to be reversible upon discontinua tion of medication, thus suggesting a possible anti-ovulato ry activity of it. When administered orally to rats on davs 1 to 7 of pregnancy, it decreased the number of fetal implantations at doses of 100 and 200 mg/kg. The extent of de crease was 33,3 and 66,6% for the respective doses. At simi lar doses, the fraction did not exhibit any abortifacient pro perty, when treated on days 9-13 of pregnancy. At 200 mg/kg dose, it however, impaired fetal growth. The fraction (100 mg/kg po) was found to be devoid of either estrocjenic or antioestrogenic property in immature rats. In isolated rat uterus, the fraction (0,05-0,4 mg/ml) inhibited the contractile responses evoked by acetyl ______________________________ y choline (5,5 x 10 M), bradykinin (1,89 x 10 M), oxytocin * (2,98 x 10 12M), BaCl2 (1,5 x 10 ~M), serotonin (2,84 x -6 -4 10 M) and KC1O (1 x 10 M) in a concentraiion dependent manner. The order of inhibition for the different agonists was as follows: BRADYKININ OXYTOCIN ACETYLCHOLINE BaCl2> SEROTONIN. A tendency to overcome its inhibitory effect was however, observed when calcium concentration in the nutrient fluid was enhanced by 2 to 3 fold. In isolated toad rectus abdominis, the fraction produced concentration de- _7 pendent inhibition of acetylcholine (1,1 x 10 M) evoked responses but did not modify the contractile responses evo- -4 -2 ked by KC12 (4 x 10 M) and caffeine (3 x 10 M). The fraction produced no significant effect on histamine (3,45 x xxii 10 M) evoked contractile responses of isolated guinea-pig ileum. The possible mechanisms involvcd in the observed pharmacoloqical properties of the fraction were discussed in relation to known biochemical effects of cucurbitacins in general. The study provided a scientific validation of the traditional use of the rhizome of Wilbrandia (cf) verticillata in arthritis and related disorders and suggest that it may be a useful alternative to presently available anti-inflammatory drugs. The anti-implantation and antiovulatory effects observed in plant preparation treated animais merit further study to explore the possibility of developing an oral contraceptive drug of plant origin.