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Title

Hypothermic activity of repin, a sesquiterpene lactone from Centaurea solstitialis

Date of Award

1993

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Abstract

Powdered aerial parts of the weed yellow starthistle (Centaurea solstitialis, Compositae) and the methanol extract, alkaloidal and fatty fractions of the methanol extract of the aerial parts, injected intraperitoneally, produced a highly significant hypothermia in conscious normal rats. Other significant symptomatology included sedation, decreases in spontaneous motor activity, depressed respiration, mydriasis, ear blanching, enophthalmos and anuria. Four sesquiterpene lactones of the guaianolide type (repin, solstitialin-A, janerin and cynaropicrin), constituents of yellow starthistle, showed similar activities in rats. The predominant effects were hypothermia, sedation and enophthalmos. Both repin and janerin, in equidoses of 3.1-31 mg/kg, produced similar profiles of generalized effects and hypothermia, whereas solstitialin-A and cynaropicrin did not show well-defined dose-response relationships. The lethal doses of the methanol extract, repin, solstitialin-A, janerin and cynaropicrin were 1000, 31, 310, 31 and 310 mg/kg, respectively. Studies were carried out to document the effects of various potential antagonists and agonists on the repin-induced hypothermic effect. Rats were pretreated intraperitoneally with atropine sulfate (10 and 20 mg/kg), atropine methylbromide (20 mg/kg), propranolol (10 and 20 mg/kg), metergoline (0.5 mg/kg), ketanserin tartrate (0.2 mg/kg), diphenhydramine HCl (10 mg/kg) and apomorphine HCl (0.5 mg/kg). No significant effects of pretreatment were evident up to 2 h but statistically significant partial reversals of repin-induced hypothermia by atropine sulfate (20 mg/kg), metergoline, ketanserin, diphenhydramine and apomorphine were observed beginning 3 h after repin injection. Propranolol pretreatment resulted in a significant potentiation of repin's hypothermic effect. The sleeping time in mice induced by intraperitoneal sodium pentobarbital was markedly potentiated by pretreatment with repin. Receptor binding studies showed that repin facilitated the binding of GABA$\sb{\rm A},$ bombesin and neuropeptide Y without any significant binding of repin to any of the 36 receptors and binding sites tested.

Pages

252

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