Nader Pestechian
Somayeh Abedi-Madiseh
Mustafa Ghanadian
Mehdi Nateghpour

Introduction: In malaria treatment protocols, treatment failure or drug resistance of synthesized drugs like alkaloids related to quinine, and aminoquinolines are the main problems now. Therefore, discovering efficient drugs or combination therapy of blood schizonticidal drugs with different mechanisms or different targets in the parasite is a crucial effort to solve this problem. In this study, the effectiveness of Crocus sativus Stigma (saffron) individually and in combination with chloroquine, was considered against chloroquine–sensitive strain of Plasmodium berghei.Methods: At the first stage, using ۴ day suppressive Peter’s test in mice, ED۵۰ and survival times of saffron methanol extract, and its aqueous and ethyl acetate fractions and chloroquine on P. berghei were calculated. Then, based on the toxicity and survival time results, combination therapy was conducted with the best saffron fraction and chloroquine against the parasite.Results: The saffron extract, aqueous and ethyl acetate fractions resulted in suppression of parasitemia with ED۵۰ values of ۵۸۷.۰ ± ۷۸.۷, ۳۲۳.۷ ± ۳۷.۲, and ۵۰۸.۷ ± ۳۵.۶ mg/kg, respectively. Combination of ethyl acetate fraction with chloroquine, potentiated the antimalarial property and the survived percent of the treated mice on days ۷, ۱۴, and ۲۸ significantly more than chloroquine or ethyl acetate fraction alone.Conclusion: Saffron and its fractions individually can be effective in reducing the parasitemia in mice. The outcome of combination of ethyl acetate fraction with chloroquine on the mice showed synergistic effect on the chloroquine–sensitive strain of parasite.