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Investigation of the Cytotoxic Effects of Momordica Charantina Extract on Leishmania Parasites with Amphotericin B and Miltefosine Drug Combinations

Year 2024, Volume: 39 Issue: 1, 1 - 7, 28.03.2024
https://doi.org/10.21605/cukurovaumfd.1459307

Abstract

Leishmaniasis is a tropical disease caused by Leishmania parasites. It is known that L. infantum causes visceral leishmaniasis (VL), which is the deadliest form of the disease, popularly known as "kala-azar". Antileishmanial agents are already available in the market, but these chemotherapeutic agents are known to have toxicities and side effects. Interest in medicinal plants and their extracts is increasing day by day, with almost no side effects. In this study, bitter melon (Momordica charantina) extracts with rich chemical content and exhibiting anti-leishmanial properties were used to develop an effective drug formulation for leishmaniasis. In the study, the cytotoxic effect of bitter melon extracts alone or in combination with different antileishmanial drugs (Amphotericin B and miltefosine) was investigated in RAW 264.7 macrophage cells. In addition, the lethal activity of the obtained extract-drug formulations on L. infantum parasite cells was also investigated by MTT analysis method. According to the data obtained from the study, it was determined that the extract did not have a toxic effect alone, when combined with the drug, it reduced the toxic effect of the drug on the cells of the innate immune system, and increased the cytotoxic effect on the leishmania parasites. It is thought that the results obtained will help to develop a treatment approach against VL.

References

  • 1. Bortolotti, M., Mercatelli, D., Polito, L., 2019. Momordica charantia, a Nutraceutical Approach for Inflammatory Related Diseases. Front Pharmacol, 10, 486.
  • 2. Wang, S., Li, Z., Yang, G., Ho, C. T., Li, S., 2017. Momordica charantia: A Popular Health-Promoting Vegetable With Multifunctionality. Food Funct, 8(5), 1749-1762.
  • 3. Jia, S., Shen, M., Zhang, F., Xie, J., 2017. Recent Advances in Momordica charantia: Functional Components and Biological Activities. Int J Mol Sci, 18(12), 2555.
  • 4. Gupta, S., Raychaudhuri, B., Banerjee, S., Das, B., Mukhopadhaya, S., Datta, S.C., 2010. Momordicatin Purified From Fruits of Momordica charantia is Effective to Act as a Potent Antileishmania Agent. Parasitol Int, 59(2), 192-197.
  • 5. Torres-Guerrero, E., Quintanilla-Cedillo, M.R., Ruiz-Esmenjaud, J., Arenas, R., 2017. Leishmaniasis: A Review. F1000Res, 6, 750.
  • 6. Kelleci, K., Allahverdiyev, A., Bağirova, M., Ihlamur, M., Abamor, E.Ş., 2023. Particulate and Non-Particle Adjuvants in Leishmaniasis Vaccine Designs: A Review. Journal of Vector Borne Diseases, 60(2), 125-141.
  • 7. Kelleci, K., 2022. Determination of Immunostimulatory Efficacy of Benzimidazole Derivatives Against Leishmania infantum. Systematic Reviews in Pharmacy, 13(12), 11.
  • 8. Monzote, L., Piñón, A., Setzer, W.N., 2014. Antileishmanial Potential of Tropical Rainforest Plant Extracts. Medicines, 1(1), 32-55.
  • 9. Saeed, F., Afzaal, M., Niaz, B., Arshad, M., Tufail, T., Hussain, M., Javed, A., 2018. Bitter Melon (Momordica charantia): A Natural Healthy Vegetable. International Journal of Food Properties, 21.
  • 10. Horax, R., Hettiarachchy, N., Chen, P., 2010. Extraction, Quantification, and Antioxidant Activities of Phenolics from Pericarp and Seeds of Bitter Melons (Momordica charantia) Harvested at Three Maturity Stages (Immature, Mature, and Ripe). J Agric Food Chem, 58(7), 4428-4433.
  • 11. Philippeos, C., Hughes, R.D., Dhawan, A., Mitry, R.R., 2012. Introduction to Cell Culture. Methods Mol Biol, 806, 1-13.
  • 12. Castelli, G., Galante, A., Lo Verde, V., Migliazzo, A., Reale, S., Lupo, T., Bruno, F., 2014. Evaluation of Two Modified Culture Media for Leishmania infantum Cultivation Versus Different Culture Media. J Parasitol, 100(2), 228-230.
  • 13. Guevara, I., Iwanejko, J., Dembińska-Kieć, A., Pankiewicz, J., Wanat, A., Anna, P., Szczudlik, A., 1998. Determination of Nitrite/Nitrate in Human Biological Material by The Simple Griess Reaction. Clin Chim Acta, 274(2), 177-188.
  • 14. Poddar, S., Sarkar, T., Choudhury, S., Chatterjee, S., Ghosh, P., 2020. Indian Traditional Medicinal Plants: A Concise Review. International Journal of Botany Studies, 5(5), 174-190.
  • 15. Oryan, A., 2015. Plant-Derived Compounds in Treatment of Leishmaniasis. Iranian Journal of Veterinary Research, 16(1), 1.
  • 16. Kelleci, K., 2023. In Vitro Anticarcinogenic, Antiparasitic and Antimicrobial Effects of P. granatum Extract. Biology Bulletin Reviews, 13(Suppl 3), 264-269.
  • 17. Haldar, A.K., Sen, P., Roy, S., 2011. Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions. Mol Biol Int, 2011, 1-23.
  • 18. Jeddi, F., Piarroux, R., Mary, C., 2011. Antimony Resistance in Leishmania, Focusing on Experimental Research. J Trop Med, 2011, 1-15.
  • 19. Kelleci, K., Gölebatmaz, E., 2023. In Vitro Determination of Antileshmanial Activities of Benzimidazolium Derivatives on L. major Promastigotes and Amastigotes. Acta Parasitologica, 68(1), 51-55.

Momordica Charantina Ekstraktının Amfotericin B ve Miltefosin İlaç Kombinasyonları ile Leishmania Parazitleri Üzerindeki Sitotoksik Etkilerinin İncelenmesi

Year 2024, Volume: 39 Issue: 1, 1 - 7, 28.03.2024
https://doi.org/10.21605/cukurovaumfd.1459307

Abstract

Leishmaniasis, Leishmania parazitlerinin neden olduğu tropikal bir hastalıktır. Halk arasında “kala-azar” olarak bilinen, hastalığın en ölümcül formu olan viserial leishmaniasise (VL) L. infantum’un neden olduğu bilinmektedir. Piyasada hali hazırda antileishmanial ajanlar mevcuttur, ancak bu kemoterapötik ajanların toksisitelerinin ve yan etkilerinin olduğu bilinmektedir. Şifalı bitkiler ve onların ekstraktlarına olan ilgi, yan etkilerinin yok denecek kadar az olmasıyla her geçen gün artmaktadır. Bu çalışmada leishmaniasise yönelik etkin bir ilaç formülasyonu geliştirmek için, zengin kimyasal içeriğe sahip, anti-leishmanial özellik sergileyen kudret narı (Momordica charantina) özütleri kullanılmıştır. Çalışmada kudret narı ekstraktları tek başına ve farklı antileishmanial ilaçlarla (Amfoterisin B ve miltefosin) kombine edilerek RAW 264.7 makrofaj hücrelerinde sitotoksik etkisi araştırılmıştır. Ayrıca elde edilen ekstrakt-ilaç formülasyonlarının L. infantum parazit hücreleri üzerindeki öldürücü etkinliği de MTT analiz yöntemi ile incelenmiştir. Çalışmadan elde edilen verilere göre ekstraktın tek başına toksik etkisinin olmadığı, ilaçla kombine edildiği zaman doğal immün sistem hücreleri üzerinde ilacın toksik etkisini azalttığı, leishmania parazitleri üzerinde ise sitotoksik etkisini arttırdığı belirlenmiştir. Elde edilen sonuçların VL karşı tedavi yaklaşımının geliştirilmesine yardımcı olacağı düşünülmektedir.

References

  • 1. Bortolotti, M., Mercatelli, D., Polito, L., 2019. Momordica charantia, a Nutraceutical Approach for Inflammatory Related Diseases. Front Pharmacol, 10, 486.
  • 2. Wang, S., Li, Z., Yang, G., Ho, C. T., Li, S., 2017. Momordica charantia: A Popular Health-Promoting Vegetable With Multifunctionality. Food Funct, 8(5), 1749-1762.
  • 3. Jia, S., Shen, M., Zhang, F., Xie, J., 2017. Recent Advances in Momordica charantia: Functional Components and Biological Activities. Int J Mol Sci, 18(12), 2555.
  • 4. Gupta, S., Raychaudhuri, B., Banerjee, S., Das, B., Mukhopadhaya, S., Datta, S.C., 2010. Momordicatin Purified From Fruits of Momordica charantia is Effective to Act as a Potent Antileishmania Agent. Parasitol Int, 59(2), 192-197.
  • 5. Torres-Guerrero, E., Quintanilla-Cedillo, M.R., Ruiz-Esmenjaud, J., Arenas, R., 2017. Leishmaniasis: A Review. F1000Res, 6, 750.
  • 6. Kelleci, K., Allahverdiyev, A., Bağirova, M., Ihlamur, M., Abamor, E.Ş., 2023. Particulate and Non-Particle Adjuvants in Leishmaniasis Vaccine Designs: A Review. Journal of Vector Borne Diseases, 60(2), 125-141.
  • 7. Kelleci, K., 2022. Determination of Immunostimulatory Efficacy of Benzimidazole Derivatives Against Leishmania infantum. Systematic Reviews in Pharmacy, 13(12), 11.
  • 8. Monzote, L., Piñón, A., Setzer, W.N., 2014. Antileishmanial Potential of Tropical Rainforest Plant Extracts. Medicines, 1(1), 32-55.
  • 9. Saeed, F., Afzaal, M., Niaz, B., Arshad, M., Tufail, T., Hussain, M., Javed, A., 2018. Bitter Melon (Momordica charantia): A Natural Healthy Vegetable. International Journal of Food Properties, 21.
  • 10. Horax, R., Hettiarachchy, N., Chen, P., 2010. Extraction, Quantification, and Antioxidant Activities of Phenolics from Pericarp and Seeds of Bitter Melons (Momordica charantia) Harvested at Three Maturity Stages (Immature, Mature, and Ripe). J Agric Food Chem, 58(7), 4428-4433.
  • 11. Philippeos, C., Hughes, R.D., Dhawan, A., Mitry, R.R., 2012. Introduction to Cell Culture. Methods Mol Biol, 806, 1-13.
  • 12. Castelli, G., Galante, A., Lo Verde, V., Migliazzo, A., Reale, S., Lupo, T., Bruno, F., 2014. Evaluation of Two Modified Culture Media for Leishmania infantum Cultivation Versus Different Culture Media. J Parasitol, 100(2), 228-230.
  • 13. Guevara, I., Iwanejko, J., Dembińska-Kieć, A., Pankiewicz, J., Wanat, A., Anna, P., Szczudlik, A., 1998. Determination of Nitrite/Nitrate in Human Biological Material by The Simple Griess Reaction. Clin Chim Acta, 274(2), 177-188.
  • 14. Poddar, S., Sarkar, T., Choudhury, S., Chatterjee, S., Ghosh, P., 2020. Indian Traditional Medicinal Plants: A Concise Review. International Journal of Botany Studies, 5(5), 174-190.
  • 15. Oryan, A., 2015. Plant-Derived Compounds in Treatment of Leishmaniasis. Iranian Journal of Veterinary Research, 16(1), 1.
  • 16. Kelleci, K., 2023. In Vitro Anticarcinogenic, Antiparasitic and Antimicrobial Effects of P. granatum Extract. Biology Bulletin Reviews, 13(Suppl 3), 264-269.
  • 17. Haldar, A.K., Sen, P., Roy, S., 2011. Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions. Mol Biol Int, 2011, 1-23.
  • 18. Jeddi, F., Piarroux, R., Mary, C., 2011. Antimony Resistance in Leishmania, Focusing on Experimental Research. J Trop Med, 2011, 1-15.
  • 19. Kelleci, K., Gölebatmaz, E., 2023. In Vitro Determination of Antileshmanial Activities of Benzimidazolium Derivatives on L. major Promastigotes and Amastigotes. Acta Parasitologica, 68(1), 51-55.
There are 19 citations in total.

Details

Primary Language Turkish
Subjects Bioengineering (Other)
Journal Section Articles
Authors

Kübra Kelleci 0000-0002-9409-2254

Murat Ihlamur 0000-0002-0458-5638

Melisa Özkan 0000-0002-5899-6037

Emrah Şefik Abamor 0000-0002-9174-4528

Publication Date March 28, 2024
Published in Issue Year 2024 Volume: 39 Issue: 1

Cite

APA Kelleci, K., Ihlamur, M., Özkan, M., Abamor, E. Ş. (2024). Momordica Charantina Ekstraktının Amfotericin B ve Miltefosin İlaç Kombinasyonları ile Leishmania Parazitleri Üzerindeki Sitotoksik Etkilerinin İncelenmesi. Çukurova Üniversitesi Mühendislik Fakültesi Dergisi, 39(1), 1-7. https://doi.org/10.21605/cukurovaumfd.1459307