Docosahexaenoic acid is potent against the growth of mature stages of Plasmodium falciparum; inhibition of hematin polymerization a possible target.

Abstract

The present study investigates the potential effect of externally added unsaturated fatty acids on P. falciparum growth. Our results indicate that polyunsaturated fatty acids (PUFAs) inhibit the growth of Plasmodium in proportional to their degree of unsaturation. At higher concentration the PUFA Docosahexaenoic acid (DHA) induces pyknotic nuclei in infected erythrocytes. When Plasmodium stages were treated transiently with DHA, the ring stage culture recovered from the drug effect and parasitemia was increased post DHA removal with delayed growth of 12h, compared to untreated control. Schizont stage treated culture displayed a 36h delay in growth to infect fresh erythrocytes signifying its recovery is less than the ring stage. However the trophozoite stage failed to recover and showed a decrease in parasitemia, similar to that of continuous treated culture. PUFAs inhibited β- hematin polymerization by binding to free heme derived from hemoglobin degradation. Digestive vacuole neutral lipid bodies, which are pivotal for β- hematin polymerization, decreased and subsequently abrogated with increasing concentration of DHA in trophozoite stage treated culture. Our study concludes that DHA interacts with heme monomers and inhibits the β- hematin polymerization and growth of mature stages i.e., trophozoite and schizont stages of plasmodium.