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Macrovipera lebetina obtusa (Dwigubsky, 1832) and Montivipera xanthina (Gray, 1849) (Ottoman Viper) are viper snakes from Viperidae family and found in various locations in Anatolia. Both snakes are responsible for major snake bite cases in Turkey Their venoms cause necrosis, hemorrhage, pain and local edema.Centaurea L. (Asteraceae) species draw attention as potential anti-inflammatory sources due to their traditional uses and accomplished studies on this field. C. calolepis Boiss. is an endemic taxon distributed in Aegean and Antalya regions in Turkey. Chloroform extract of C. calolepis and its major compound cnicin, a sesquiterpene lactone, are reported to have strong anti-inflammatory activities in-vitro, by previous studies.In the present study, in-vivo anti-inflammatory activities of C. calolepis chloroform extract and the sesquiterpenoid cnicin against edema induced by Macrovipera lebetina obtusa and Montivipera xanthina venoms were evaluated in the rat model. Protein contents and induction doses of the venoms were determined. Carrageenan and snake venoms were used as inducing agents in paw edema tests.Extract demonstrated strong inhibition on edema at all doses and hours against M. xanthina venom and carrageenan. Inhibition ratio of extract at 25 mg/kg dose (84.13% inhibition) after 0.5 h M. xanthina venom injection was more than indomethacin's value (45.4% inhibition). The extract also showed significant effect also on inflammation caused by M. lebetina obtusa venom at all doses. However, 2.5 mg/kg cnicin was more effective than total extract of C. calolepis against rat paw edema induced by (27.31%) M. lebetina obtusa venom.This is the first study reported therapeutic potential of C. calolepis, an endemic plant of Turkey, in case of snake-bites cause inflammation by venomous species in natural fauna of Anatolia.C. calolepis exhibited strong activity against M. xanthina-induced and carrageenan-induced edema in the rat.2.5 mg/kg cnicin was found to be more effective than C. calolepis on paw edema induced by M. lebetina obtusa venom.This is the first study on therapeutic potential of C. calolepis, an endemic plant of Turkey, in case of snake bite.