Cuscuta reflexa Possess Potent Inhibitory Activity Against Human Malaria Parasite: An In Vitro and In Vivo Study.

Drug resistance to practically all antimalarial drugs in use necessitate the development of new chemotherapeutics against malaria. In this aspect, traditionally used plants with folklore reputation are the pillar for drug discovery. Cuscuta reflexa being traditionally used in the treatment of malaria in Odisha, India we aimed to experimentally validate its antimalarial potential. Different solvent extracts of C. reflexa or column fractions from a promising solvent extract were evaluated for in vitro anti-plasmodial activity against Plasmodium falciparum strain Pf3D7. Potent fractions were further evaluated for inhibition of parasite growth against different drug resistant strains. Safety of these fractions was determined by in vitro cyto-toxicity, and therapeutic effectiveness was evaluated by suppression of parasitemia and improvement in survival of experimental mice. Besides, their immunomodulatory effect was investigated in Pf-antigen stimulated RAW cells. GCMS fingerprints of active fractions was determined. Column separation of methanol extract which showed the highest in vitro antiplasmodial activity (IC50 = 14.48 µg/ml) resulted in eleven fractions, three of which (F2, F3, and F4) had anti-plasmodial IC50 ranging from ≤ 10 to 2.2 µg/ml against various P. falciparum strains with no demonstration of in vitro cytotoxicity. F4 displayed the highest in vivo parasite suppression, and had a mean survival time similar to artesunate (19.3 vs. 20.6 days). These fractions significantly modulated expression of inflammatory cytokines in Pf-antigen stimulated RAW cells. The findings of the study confirm the antimalarial potential of C. reflexa. Exploration of phyto-molecules in GCMS fingerprints of active fractions is warranted for possible identification of lead anti-malarial phyto-drugs.

Effect of Plasmodium falciparum infection on blood parameters and their association with clinical severity in adults of Odisha, India.

The extent of abnormalities in blood indices and their subsequent effects on clinical severity in malaria differ among populations of different endemicity. However, these alterations have not been well investigated in Odisha, India and their prognostic implications in the context of multi-organ dysfunction (MODS) in severe malaria (SM) are not identified so far. The present study was carried out in 200 adult patients each from uncomplicated malaria and severe malaria groups to examine whether host haematological and biochemical parameters in Plasmodium falciparum infection can act as diagnostic marker for SM in adults patients of Odisha. The results showed thrombocytopenia as a potential risk factor for SM irrespective of disease features with least median platelet counts observed in patients with MODS (Platelet count: 144.5, P = < 0.0001) compared to mild malaria. Logistic regression analysis identified anemia (<10 mg/dl) as independent predictor of MODS (OR = 12.78, 95% CI = 4.93-33.2). The prognostic utility of thrombocytopenia (platelet count: ≤100,000/µl) as marker of MODS was largely modulated by hemoglobin and blood glucose level. Co-existence of hypoglycemia and thrombocytopenia was also observed. Our study revealed changes in blood indices such as low platelet, hemoglobin and blood glucose during falciparum infection in adults can be used as diagnostic criteria for predicting SM in combinations. The study also provides important clue for plausible hypoglycemia mediated platelet necrosis and clearance. Further studies in different endemic regions need to be conducted for validation of these findings and their implication as criteria for diagnosing SM in adults.