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

Abstract

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 antileishmanial efficacy of purified chlorogenic acid (CGA) against promastigotes and intracellular amastigotes infected into RAW264.7 macrophages. Methods and Results Chlorogenic acid was effective both on promastigotes (IC50 = 78.394 µmol/L, i.e. 27.75 µg/mL) and intracellular amastigotes (ED50 = 26.752 µmol/L, 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. Flow cytometric 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 µmol/L (21.24 µg/mL) CGA for 24 hours, with negligible toxicity to host macrophages. This parasite clearing efficacy was comparable to 1.0 µg/mL (1.082 µmol/L) Amphotericin B, and 20 µmol/L Miltefosine, two standard antileishmanial 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 Chlorogenic acid might emerge as a potential antileishmanial drug.

Repurposing the Antibacterial Agents Peptide 19-4LF and Peptide 19-2.5 for Treatment of Cutaneous Leishmaniasis

“…It has been demonstrated that Leishmania clearance was enhanced by the Th1-type response, in which IL-12 expression played a crucial role [49]. Consistent with this, an increase in IL-12, TNF and NO production by macrophages was shown to be characteristic of an efficient anti-parasitic response [50]. In addition, immunotherapy with IL-12 was reported to mediate the control of L. major infection in BALB/c mice and was associated with wound healing promotion, parasite burden reduction and IL-4 downregulation [43].…”

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review

“…After 48 h of CGA treatment, the protoflagella of Leishmania changed into a spherical shape, the flagella disappeared, the exercise capacity decreased, the metabolic activity decreased, and the growth reversed. In the logarithmic phase, the researchers discovered that the growth of flagella at the G1/S checkpoint was significantly blocked ( 87 ). Fusarium is one of the causes of rot and spoilage of fruits and vegetables.…”

Bioactive functions of chlorogenic acid and its research progress in pig industry

“…In addition, CGA could exert antifungal effects on Candida albicans by affecting fungal cell membranes (Sung & Lee, 2010). Additionally, it was reported that CGA could inhibit Leishmania , indicating that CGA may be a potential antiparasitic drug (Majumder et al, 2020). Wang et al (2017) reported that CGA could inhibit liver fibrosis induced by schistosomiasis and may serve as an antifibrotic drug for schistosomiasis liver fibrosis.…”