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

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Abstract

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.

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Acknowledgements

We thankfully acknowledge the financial support from Science and Technology Department, Govt. of Odisha to GD and from Drug and Pharmaceuticals Research Programe (DPRP) to SS. SBO is supported by DST-INSPIRE fellowship. We sincerely thank Advanced Instrumentation and Research Facility (AIRF), JNU, New Delhi for providing the facility of GCMS/MS. We thank Central Instrumentation Facility (CIF) of Special Centre for Molecular Medicine (SCMM), JNU New Delhi.

Funding

This study is supported by the Science and Technology Department, Govt. of Odisha to GD (27552800232014/20) and from Drug and Pharmaceuticals Research Program to SS (P/569/2016–1/TDT, SS).

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Authors and Affiliations

  1. Department of Biotechnology, Maharaja Sriram Chandra Bhanja Deo University, Baripada, Odisha, 757003, India

    Sashi Bhusan Ojha, Shaktirekha Roy & Gunanidhi Dhangadamajhi

  2. Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India

    Raj Kumar Sah, Evanka Madan, Ruby Bansal & Shailja Singh

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  1. Sashi Bhusan Ojha
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  2. Raj Kumar Sah
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  3. Evanka Madan
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  7. Gunanidhi Dhangadamajhi
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Contributions

Conceptualization, GD and SS; Methodology, SS, GD, SBO and RS; Investigation, SBO, RS, EM, RB and SR; Writing- original draft, SBO, GD and SS; Writing-review and editing, SS and GD. Funding acquisition, SS and GD; Supervision, SS and GD. All authors contributed to the article and approved the submitted version.

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Correspondence to Shailja Singh or Gunanidhi Dhangadamajhi.

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Ojha, S.B., Sah, R.K., Madan, E. et al. Cuscuta reflexa Possess Potent Inhibitory Activity Against Human Malaria Parasite: An In Vitro and In Vivo Study. Curr Microbiol 80, 189 (2023). https://doi.org/10.1007/s00284-023-03289-x

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