Chlorogenic acid acts upon Leishmania donovani arresting cell cycle and modulating cytokines and nitric oxide in vitro

Nilanjana Majumder, Subhrajit Ganguly, Arijit Kumar Ghosh, Shreetoma Kundu, Antara Banerjee, Samiran Saha
Parasite Immunology 2020 April 5, : e12719

AIMS: Visceral leishmaniasis (VL), caused by Leishmania donovani in India, is fatal if untreated, having serious concern of limited chemotherapeutic options. In this study, we evaluated anti-leishmanial efficacy of purified chlorogenic acid (CGA) against promastigotes and intracellular amastigotes infected into RAW264.7 macrophages.

METHODS AND RESULTS: CGA was effective both on promastigotes (IC50 =78.394 µM i.e. 27.75 µg/mL) and intracellular amastigotes (ED50 =26.752 µM i.e. 9.47 µg/mL). In promastigotes, significant retardation in mitotic growth was caused both by cell-death and reduction of metabolic activity, evidenced by propidium-iodide uptake and MTT assay respectively. Flowcytometric analysis revealed that, retardation of mitotic growth was due to cell-cycle arrest at G1/S checkpoint. Complete clearance of amastigotes from infected RAW264.7 cells, assessed by microscopic counting, was achieved with 60 µM (21.24 µg/mL) CGA for 24 h, with negligible toxicity to host macrophages. This parasite clearing efficacy was comparable to 1.0 µg/mL (1.082 µM) Amphotericin B, and 20 µM Miltefosine, two standard anti-leishmanial drugs. Cytokine-ELISA revealed that, elevated IL-10 production by infected macrophages was reduced after parasite clearance. Consequently, IL-12, TNF and NO (assayed by Griess-test) production by macrophages were significantly increased after successful resolution of infection.

CONCLUSION: CGA might emerge as a potential anti-leishmanial drug.

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