Antiplasmodial activity of papaya leaf decoction and its synergistic effects in combination with artemisinin

Within the framework of a larger research project [1] aiming at evaluating the possible synergistic effects in malaria treatment between artemisinins-one the most potent antimalarial agents- and a variety of plant extracts and isolated natural constituents, the antiplasmodial properties of a dried decoction of papaya leaf is reported. The antimalarial activity of papaya is mostly anecdotal but in literature there is a report on the efficacy of a crude aqueous extract of papaya leaf on mice infested with malaria parasite in vivo [2]. A decoction was prepared with 10g of „mature“ papaya leaf (leaf collected already dried in the plant) from Burundi, according to the traditional preparation described by local healers (boiling for several hours until concentration to half volume). After cooling the solution, leaves were filtered and the decoction was liophylised. The dried extract (2.6g) was submitted the HPLC analysis to evaluate the content of polyphenols. 1.6% of total flavonoids expressed as rutin were characterised being trisaccharides of kaempferol and quercetin. The extract of papaya inhibited 3D7 P. falciparum growth with IC50 values of 166.0±1.23µg/ml. Isobologram analysis showed that the extract of papaya, 100 or 150µg/ml, used in combination whith artemisinin, at sublethal doses, ranging from 0.625 to 40 nM, exert a strong sinergistic effect. The crude extract was submitted to a fractionation with Sephadex LH-20 to obtain, among others, three fractions (CPC, CPD and CPE) having strong activity and containing the polyphenol constituents.

Acknowledgments: The Ente Cassa di Risparmio di Firenze and Toscana Life sciences are gratefully acknowleged for generous financial supports.

References: [1] Sannella, A.R. et al. (2007) Biochem. Biophys. Res. Commun. 353:177–181.

[2] Berkelar, D. (2002) Echo Tech. Notes 71:1–4.