curcumin-arteether combination therapy of plasmodium berghei-infected mice prevents recrudescence through immunomodulationcurcumin-arteether联合治疗的疟原虫berghei-infected老鼠通过免疫调节防止复发.pdf

Curcumin-Arteether Combination Therapy of Plasmodium berghei-Infected Mice Prevents Recrudescence Through Immunomodulation 1 1 1 2 Palakkod G. Vathsala , Chaitanya Dende , Viswanathan Arun Nagaraj , Debapriya Bhattacharya , 2 1 1 Gobardhan Das , Pundi N. Rangarajan , Govindarajan Padmanaban * 1 Department of Biochemistry, Indian Institute of Science, Bangalore, India, 2 International Centre for Genetic Engineering and Biotechnology, New Delhi, India Abstract Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA), a single dose of alpha,beta- arteether (ART) with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE) or ART+curcumin (AC) treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE- treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2–3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INFc and IL-12 was observed in AC-treatment. There was a