Leaf Decoction of Carica papaya Combined with Artesunate Prevents Recrudescence in Plasmodium berghei-Infected Mice

Abstract

Malaria treatment and control have become increasingly difficult because of the spread of drug-resistant strains of Plasmodium falciparum and Plasmodium vivax. Thus, there is a continuous need to develop new combination therapies such as artemisinin-based combination therapies (ACTs) to contrast the emergence of resistant Plasmodium strains. Despite ACT has been recommended by the World Health Organization since 2001, its overall deployment in poor endemic areas is very slow, principally due to its high cost. In the malaria endemic areas, plant remedies are still widely used mostly without assurance of their efficacy and/or safety. A variety of widespread herbal drugs or natural products were already reported for their possible plasmodicidal activities, but the studies concerning their activity in combination with artemisinins are very scarce. The antimalarial activity of papaya is mostly anecdotal, and the present study is aimed at investigating the antiplasmodial activity of a decoction obtained by traditional recipe from the mature leaves of Carica papaya. The decoction was analyzed by HPLC-DAD-MS (high performance liquid chromatography coupled with diodoarray detector and mass spectrometry) showing the presence of caffeoyl derivatives and di- and triglycosides of flavonols. The extract was found to be active against P. falciparum 3D7 strains with a synergism in the presence of artemisinin. In vivo activity against the murine malaria model of Plasmodium berghei was disclosed both for the dried extract alone (250, 500, and 750 mg/kg/d) and for its combination with artesunate (250 mg/kg/d papaya plus 10 mg/kg/d artesunate). This combination displayed the greatest antimalarial activity in terms of reduction of parasitemia and prevention of recrudescence in animals recovered from the infection.

Carica papaya L. Leaf: A Systematic Scoping Review on Biological Safety and Herb-Drug Interactions

“…No unfavourable outcomes were explicitly reported with short durations of coadministration with these drugs, though it was not within the trials' objectives to investigate herb-drug interactions [ 6 , 34 , 36 , 37 , 39 – 41 , 43 , 48 , 49 ]. In preclinical studies, C. papaya leaf demonstrated significant herb-drug interaction with several drugs including metformin, glimepiride, digoxin, ciprofloxacin, and artemisinin [ 60 – 65 ]. Herb-drug interaction investigations revealed complex interactions between 96% C. papaya leaf ethanolic extract and other oral hypoglycaemic agents (metformin and glimepiride) [ 60 ].…”

“…When administered in combination with artemisinin, isobologram analysis shows subsynergism or additive antimalarial effects of C. papaya leaf decoction against Plasmodium falciparum [ 61 , 65 ]. C. papaya leaf reported antimalarial properties as a single intervention [ 65 , 77 , 78 ], which may contribute towards some pharmacodynamic additive effects, though the mechanisms remain unclear. On the other hand, C. papaya leaf crude aqueous extract demonstrated antagonistic antimalarial effects against artemisinin in Plasmodium-berghei -infected mice [ 62 ].…”

Evaluation of Antimalarial Potential of Extracts from Alstonia boonei and Carica papaya in Plasmodium berghei-Infected Mice

“…e fruit of the plant is eaten globally, while the leaves are used in some parts of the world to treat human diseases such as malaria, typhoid, piles, and diabetes. Literature search reveals scientific evidence for the antimalarial activity of C. papaya extracts when administered singly or in combination with other plant extract or with approved drugs [13][14][15][16]. C. papaya is rich in bioactive phytochemicals of diverse families.…”

“…C. papaya is rich in bioactive phytochemicals of diverse families. Glycosides of flavanols and caffeoyl derivatives obtained from the decoction of C. papaya leaves have shown synergistic potency with artesunate against P. falciparum and P. berghei, preventing parasite recrudescence [17].…”