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In vitro and in vivo therapeutic antileishmanial potential of ellagic acid against Leishmania donovani in murine model

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Abstract

Parasite of genus Leishmania viz. L. donovani and L. infantum cause visceral leishmaniasis (VL) or Kala-azar, systemic disease with significant enlargement of the liver and spleen, weight loss, anemia, fever and immunosuppression. The silent expansion of vectors, reservoir hosts and resistant strains is also of great concern in VL control. Considering all these issues, the present study focused on in vitro and in vivo antileishmanial screening of ellagic acid (EA) against L. donovani. The in vitro study was performed against the protozoan parasite L. donovani and a 50% inhibitory concentration was calculated. The DNA arrest in the sub-G0/G1 phase of the cell cycle was studied. In vivo studies included the assessment of parasite burden and immunomodulation in response to treatment of ellagic acid in BALB/c mice. The levels of Th1 and Th2 cytokines and isotype antibodies were assessed in different groups of mice. EA showed in vitro parasiticidal activity with IC50 18.55 µg/mL and thwarted cell-cycle progression at the sub-G0/G1 phase. Administration of ellagic acid to the BALB/c mice reported diminution of splenic and hepatic parasite burden coupled with an expansion of CD4+ and CD8+ T lymphocytes. EA further potentiated a protective immune response with augmentation of Th1 type immune response evidenced by elevation of serum IgG2a levels and DTH response. EA was reported to be safe and non-toxic to the THP-1 cell line as well as to the liver and kidneys of mice. These findings endorse the therapeutic potential of EA with significant immunomodulation and can serve as a promising agent against this debilitating parasitic disease.

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Acknowledgements

The authors are thankful to the DST-Central Sophisticated Instrument Cell, Post Graduate Institute of Medical Education and Research (CSIC, PGIMER), Chandigarh for providing instrumentation facility.

Funding

This work was financially supported by University Grants Commission, New Delhi under the grants, UGC-JRF/SRF Fellowship (3643/NET-DEC.2012) and UGC-CAS (F.4-28/2015/CAS-II) (SAP-II).

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  1. Parasitology Laboratory, Department of Zoology (UGC-CAS), Panjab University, Chandigarh, 160014, India

    Poonam Keshav, Deepak Kumar Goyal & Sukhbir Kaur

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Contributions

PK and DKG carried out the experimental work and wrote the manuscript. PK, DKG, and SK designed the study. SK supervised the experimental study and reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sukhbir Kaur.

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The ethical clearance was acquired from the Institutional Animal Ethics Committee (IAEC) of the University with IAEC no. PU/IAEC/S/14/147.

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Keshav, P., Goyal, D.K. & Kaur, S. In vitro and in vivo therapeutic antileishmanial potential of ellagic acid against Leishmania donovani in murine model. Med Microbiol Immunol 212, 35–51 (2023). https://doi.org/10.1007/s00430-022-00754-5

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