Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion

Bhimashankar Utage; Milind Patole; Punam Nagvenkar; Rajesh Gacche

doi:10.1016/j.jtcme.2023.06.003

Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion

J Tradit Complement Med. 2023 Jun 29;13(6):611-622. doi: 10.1016/j.jtcme.2023.06.003. eCollection 2023 Nov.

Authors

Bhimashankar Utage¹, Milind Patole¹, Punam Nagvenkar¹, Rajesh Gacche²

Affiliations

¹ National Centre for Cell Science, NCCS Complex, Pune, 411007, MS, India.
² Department of Biotechnology, Savitribai Phule Pune University, Pune, 411007, MS, India.

Abstract

Background: Leishmaniasis is endemic in more than 60 countries with a large number of mortality cases. The current chemotherapy approaches employed for managing the leishmaniasis is associated with severe side effects. Therefore there is a need to develop effective, safe, and cost affordable antileishmanial drug candidates.

Purpose of the study: This study was designed to evaluate the in vitro antileishmanial activity of a Prosopis juliflora leaves extract (PJLME) towards the Leishmania donovani parasites.

Material and methods: PJLME was evaluated for its cytotoxicity against the L. donovani parasites and the mouse macrophage cells. Further, various in vitro experiments like ROS assay, mitochondrial membrane potential assay, annexin v assay, cell cycle assay, and caspase 3/7 assay were performed to understand the mechanism of cell death. Phytochemical profiling of P. juliflorawas performed by utilizing HPTLC and GC-MS analysis.

Results: PJLME demonstrated antileishmanial activity at a remarkably lower concentration of IC₅₀ 6.5 μg/mL. Of note, interestingly PJLME IC₅₀ concentration has not demonstrated cytotoxicity against the mouse macrophage cell line. Performed experiments confirmed ROS inducing potential of PJLME which adversely affected the mitochondrial membrane potential and caused loss of mitochondrial membrane potential and thereby ATP levels. PJLME also arrested the cell cycle and induced apoptotic-like cell death in PJLME treated L. donovani promastigotes.

Conclusion: The results clearly established the significance of Prosopis juliflora as an effective and safe natural resource for managing visceral leishmaniasis. The findings can be used as a baseline reference for developing novel leads/formulations for effective management of visceral leishmaniasis.

Keywords: Apoptosis; Cell cycle; GC-MS; Natural products; Prosopis juliflora; Visceral leishmaniasis.