Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion
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 antilei...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Journal of Traditional and Complementary Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2225411023000755 |
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| author | Bhimashankar Utage Milind Patole Punam Nagvenkar Rajesh Gacche |
| author_facet | Bhimashankar Utage Milind Patole Punam Nagvenkar Rajesh Gacche |
| author_sort | Bhimashankar Utage |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T14:17:17Z |
| format | Article |
| id | doaj.art-7525890fc1364d04bb782795be3073f8 |
| institution | Directory Open Access Journal |
| issn | 2225-4110 |
| language | English |
| last_indexed | 2024-03-11T14:17:17Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Traditional and Complementary Medicine |
| spelling | doaj.art-7525890fc1364d04bb782795be3073f82023-11-01T04:47:19ZengElsevierJournal of Traditional and Complementary Medicine2225-41102023-11-01136611622Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletionBhimashankar Utage0Milind Patole1Punam Nagvenkar2Rajesh Gacche3National Centre for Cell Science, NCCS Complex, Pune, 411007, MS, India; Corresponding author.National Centre for Cell Science, NCCS Complex, Pune, 411007, MS, IndiaNational Centre for Cell Science, NCCS Complex, Pune, 411007, MS, IndiaDepartment of Biotechnology, Savitribai Phule Pune University, Pune, 411007, MS, India; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2225411023000755Visceral leishmaniasisNatural productsProsopis julifloraApoptosisCell cycleGC-MS |
| spellingShingle | Bhimashankar Utage Milind Patole Punam Nagvenkar Rajesh Gacche Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion Journal of Traditional and Complementary Medicine Visceral leishmaniasis Natural products Prosopis juliflora Apoptosis Cell cycle GC-MS |
| title | Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion |
| title_full | Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion |
| title_fullStr | Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion |
| title_full_unstemmed | Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion |
| title_short | Prosopis juliflora (Sw.) DC.induces apoptotic-like programmed cell death in Leishmania donovani via over production of oxidative stress, mitochondrial dysfunction and ATP depletion |
| title_sort | prosopis juliflora sw dc induces apoptotic like programmed cell death in leishmania donovani via over production of oxidative stress mitochondrial dysfunction and atp depletion |
| topic | Visceral leishmaniasis Natural products Prosopis juliflora Apoptosis Cell cycle GC-MS |
| url | http://www.sciencedirect.com/science/article/pii/S2225411023000755 |
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