Andrographolide (AND), the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plant Andrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of Plasmodium falciparum in vitro and Plasmodium berghei ANKA in vivo. IC50s for artesunate (AS), andrographolide (AND), and curcumin (CUR) were found to be 0.05, 9.1 and 17.4？μM, respectively. The compound (AND) was found synergistic with curcumin (CUR) and addictively interactive with artesunate (AS). In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%), compared to the control (81%), but also by extending the life span by 2-3 folds. Being nontoxic to the in vivo system this agent can be used as template molecule for designing new derivatives with improved antimalarial properties. 1. Introduction The discoveries leading to information on novel drugs and drug combinations have become a priority to manage the increasing burden of malaria, caused by drug resistant parasites. Artemisinin derivative-based drug combinations that have independent mode of action are seen as a way of enhancing efficacy and simultaneously ensuring protection against resistance [1, 2] among the parasites. The anti-malarial properties of a tropical plant Andrographis paniculata has been studied in details recently by Mishra et al. [3], and also, there are several reports that demonstrate the antimalarial properties of the plant A. paniculata [4–6], but there is hardly any report that describe the active compound responsible for the anti-malarial property of this plant. Andrographolide, the diterpenic lactone compound, is one of the major phytoconstituents of the plant A. paniculata and has been reported to have diverse pharmacological potential including antiviral [7], anti-inflammatory [8–11], and anticancer properties [12]. The present study for the first time establishes andrographolide as the major bioactive anti-malarial constituent of the plant A. paniculata using both in vitro and in vivo approaches. The encouraging in vitro antiplasmodial activities of andrographolide prompted us to evaluate the interaction of andrographolide (AND) with other established anti-malarial compounds such as curcumin (CUR) and artesunate (AS), the hemisuccinate derivative of artemisinin in vitro on Plasmodium falciparum, and in vivo on Plasmodium berghei ANKA strains. This adds new information on combination of potent anti-malarial
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