Antileishmanial Activity of Quercetin-ZnMgFe2O4 Nanostructure on Leishmania major in Vitro
,
Abstract
Background: Cutaneous leishmaniasis is a neglected parasitic disease prevalent in tropical and subtropical regions, caused by different species of the genus Leishmania. Current therapeutic options are limited due to toxicity, prolonged treatment regimens, and emerging drug resistance.
Methods: This study was conducted at Kashan University of Medical Sciences, Kashan, Iran in 2024. The antileishmanial activity of quercetin and a synthesized quercetin–ZnMgFe₂O₄ nanostructure was evaluated against L. major promastigotes in vitro conditions. The nanostructure was synthesized and characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The antileishmanial activity was assessed by determining the mortality rate of promastigotes at different concentrations (150, 300, 450, and 600 μg/mL) of quercetin and also quercetin–ZnMgFe₂O₄ nanostructure. In addition, ultrastructural and nuclear alterations were examined following exposure to 150 and 600 μg/mL of both quercetin and the nanostructure.
Results: The quercetin–ZnMgFe₂O₄ nanostructure exhibited significantly higher inhibitory activity compared with quercetin. The mortality rates for the nanostructure were 73% and 85.9% at 150 and 600 μg/mL, respectively, compared with 42% and 81% for quercetin. Microscopic analysis revealed pronounced morphological alterations, including damage to the cell body and flagella, as well as destruction of the nucleus and kinetoplast.
Conclusion: The Quercetin_ZnMgFe₂O₄ nanostructure exhibited considerable antileishmanial activity against L.major promastigotes in vitro. Considering the obtained results, this nanostructure can be considered in anti-leishmanial studies and further in vitro and in vivo investigations are required to evaluate its safety and efficacy.
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3. Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016; 15;63(12):1539-1557.
4. Blum J, Desjeux P, Schwartz E, et al. Treatment of cutaneous leishmaniasis among travellers. J Antimicrob Chemother. 2004;53(2):158–66.
5. Aronson NE, Joya CA. Cutaneous Leishmaniasis: Updates in Diagnosis and Management. Infect Dis Clin North Am. 2019;33(1):101–17.
6. Batiha GE, Beshbishy AM, Ikram M, et al. The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin. Foods. 2020;9(3):374
7. Cataneo AHD, Tomiotto-Pellissier F, Miranda-Sapla MM, et al. Quercetin promotes antipromastigote effect by increasing the ROS production and anti-amastigote by upregulating Nrf2/HO-1 expression, affecting iron availability. Biomed Pharmacother. 2019:113:108745.
8. Mehwish S, Khan H, Rehman AU, et al. Natural compounds from plants controlling leishmanial growth via DNA damage and inhibiting trypanothione reductase and trypanothione synthetase: an in vitro and in silico approach. 3 Biotech. 2019;9(8):303.
9. Vila-Nova NS, Morais SM, Falcão MJC, et al. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome. Pesqui Vet Bras. 2012;32(11):1164–8.
10. Mohajeri M, Saghaei L, Ghanadian M, et al. Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives. Adv Biomed Res. 2018;7(1):64.
11. Memariani H, Memariani M, Ghasemian A. Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues. Biomed Res Int. 2024;2024.
12. Alanazi AD, Said M Ben. Plant Bioactive Ingredients in Delivery Systems and Nanocarriers for the Treatment of Leishmaniasis: An Evidence-Based Review. Iran J Parasitol. 2022;17(4):458-72.
13. Oryan A, Bemani E, Bahrami S. Anti-leishmanial, immunomodulatory and anti-oxidative activity of quercetin against cutaneous leishmaniasis caused by Leishmania major. Asian Pac J Trop Biomed. 2023;13(1):26–34.
14. Da Silva ER, Maquiaveli C do C, Magalhães PP. The leishmanicidal flavonols quercetin and quercitrin target Leishmania (Leishmania) amazonensis arginase. Exp Parasitol. 2012;130(3):183–8.
15. Fonseca-Silva F, Inacio JDF, Canto-Cavalheiro MM, et al. Reactive oxygen species production by quercetin causes the death of Leishmania amazonensis intracellular amastigotes. J Nat Prod. 2013;76(8):1505–8.
16. Mehwish S, Varikuti S, Ali Khan M, et al. Bioflavonoid-Induced Apoptosis and DNA Damage in Amastigotes and Promastigotes of Leishmania donovani: Deciphering the Mode of Action. Molecules. 2021;26(19):5843.
17. AbouLaila M, Abdelaziz A, Rizk M, et al. Evaluation of the in vitro and in vivo inhibitory effects of quercetin on the growth of Babesia and Theileria parasites. Damanhour J Vet Sci. 2019;2(1):23–7.
18. Khalid SA, Farouk A, Geary TG, et al. Potential antimalarial candidates from African plants: and in vitro approach using Plasmodium falciparum. J Ethnopharmacol. 1986;15(2):201–9.
19. Freitas RF, Prokopczyk IM, Zottis A, et al. Discovery of novel Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase inhibitors. Bioorg Med Chem. 2009; 17(6):2476–82.
20. Tasdemir D, Kaiser M, Brun R, et al. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob Agents Chemother. 2006;50(4):1352–64.
21. Mohebali F, Aghabarari B, Vaezi MR, et al. Biomacromolecule chitosan carrying meglumine antimoniate coated on a silver/polyurethane nanostructure as a wound dressing: Therapeutic efficacy on cutaneous leishmaniasis caused by Leishmania major in BALB/c mice. Int J Biol Macromol. 2025;307(Pt 2).
22. Tavakoli P, Ghaffarifar F, Delavari H, et al. Synthesis of Tellurium Oxide (TeO2) Nanorods and Nanoflakes and Evaluation of Its Efficacy Against Leishmania major In vitro and In vivo. Acta Parasitol. 2022;67(1):143–52.
23. Ghaffari AD, Barati M, KarimiPourSaryazdi A, et al. In vitro and in vivo study on antiprotozoal activity of calcium oxide (CaO) and magnesium oxide (MgO) nanoparticles on promastigote and amastigote forms of Leishmania major. Acta Trop. 2023;238 :106788.
24. Saleh F, Kheirandish F, Abbasi M, et al. Comparison of biosynthetic zinc oxide nanoparticle and glucantime cytotoxic effects on Leishmania major (MRHO/IR/75/ER). J Basic Microbiol. 2024;64(5): e2300490.
25. Rahnama V, Motazedian M, Mohammadi-Samani S, et al. Artemether-loaded nanostructured lipid carriers: preparation, characterization, and evaluation of in vitro effect on Leishmania major. Res Pharm Sci. 2021;16(6):623–33.
26. Abazari R, Mahjoub AR, Molaie S, et al. The effect of different parameters under ultrasound irradiation for synthesis of new nanostructured Fe3O4@bio-MOF as an efficient anti-leishmanial in vitro and in vivo conditions. Ultrason Sonochem. 2018;43:248–61.
27. Saryazdi KA, Dalimi A, Sadeghi SH, et al. Effects of silver nanoparticle based on ginger extract on Leishmania infantum and Leishmania tropica parasites: in vitro. Arch Razi Inst. 2024;79(2):335.
28. Chaurasia M, Singh PK, Jaiswal AK, et al. Bioinspired Calcium Phosphate Nanoparticles Featuring as Efficient Carrier and Prompter for Macrophage Intervention in Experimental Leishmaniasis. Pharm Res. 2016;33(11):2617–29.
29. Allahverdiyev AM, Abamor ES, Bagirova M, et al. Antileishmanial effect of silver nanoparticles and their enhanced antiparasitic activity under ultraviolet light. Int J Nanomedicine. 2011;6:2705–14.
30. Rodrigues JM, Croft SL, Fessi H, et al. The activity and ultrastructural localization of primaquine-loaded poly (d,l-lactide) nanoparticles in Leishmania donovani infected mice. Trop Med Parasitol. 1994;45(3):223–8.
31. Özel Y, Çavuş I, Yilmaz U, et al. (Investigation of Cytotoxic and Antileishmanial Activity of Hybrid Silver Nanoparticle Complexes: Potential Drug Candidates against Leishmania Species). Mikrobiyol Bul. 2024 (2):182-195.
32. Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84–9.
33. Leopoldini M, Russo N, Chiodo S, et al. Iron chelation by the powerful antioxidant flavonoid quercetin. J Agric Food Chem. 2006;54(17):6343–51.
34. Elizondo-Luévano JH, Pérez-Narváez OA, Sánchez-García E, et al. In-Vitro Effect of Kalanchoe daigremontiana and Its Main Component, Quercetin against Entamoeba histolytica and Trichomonas vaginalis. Iran J Parasitol. 2021;16(3):394–401.
35. Guo Y, Bruno RS. Endogenous and exogenous mediators of quercetin bioavailability. J Nutr Biochem. 2015;26(3):201–10.
36. Riva A, Ronchi M, Petrangolini G, et al. Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin. Eur J Drug Metab Pharmacokinet. 2019;44(2):169-177.
37. Omi N, Shiba H, Nishimura E, et al. Effects of enzymatically modified isoquercitrin in supplementary protein powder on athlete body composition: A randomized, placebo-controlled, double-blind trial. J Int Soc Sports Nutr. 2019;16(1):39.
2. Razavi MR, Shirzadi MR, Mohebali M, et al. Human Cutaneous Leishmaniosis in Iran, Up to Date-2019. J Arthropod Borne Dis. 2021;15(2):143–51.
3. Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016; 15;63(12):1539-1557.
4. Blum J, Desjeux P, Schwartz E, et al. Treatment of cutaneous leishmaniasis among travellers. J Antimicrob Chemother. 2004;53(2):158–66.
5. Aronson NE, Joya CA. Cutaneous Leishmaniasis: Updates in Diagnosis and Management. Infect Dis Clin North Am. 2019;33(1):101–17.
6. Batiha GE, Beshbishy AM, Ikram M, et al. The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin. Foods. 2020;9(3):374
7. Cataneo AHD, Tomiotto-Pellissier F, Miranda-Sapla MM, et al. Quercetin promotes antipromastigote effect by increasing the ROS production and anti-amastigote by upregulating Nrf2/HO-1 expression, affecting iron availability. Biomed Pharmacother. 2019:113:108745.
8. Mehwish S, Khan H, Rehman AU, et al. Natural compounds from plants controlling leishmanial growth via DNA damage and inhibiting trypanothione reductase and trypanothione synthetase: an in vitro and in silico approach. 3 Biotech. 2019;9(8):303.
9. Vila-Nova NS, Morais SM, Falcão MJC, et al. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome. Pesqui Vet Bras. 2012;32(11):1164–8.
10. Mohajeri M, Saghaei L, Ghanadian M, et al. Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives. Adv Biomed Res. 2018;7(1):64.
11. Memariani H, Memariani M, Ghasemian A. Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues. Biomed Res Int. 2024;2024.
12. Alanazi AD, Said M Ben. Plant Bioactive Ingredients in Delivery Systems and Nanocarriers for the Treatment of Leishmaniasis: An Evidence-Based Review. Iran J Parasitol. 2022;17(4):458-72.
13. Oryan A, Bemani E, Bahrami S. Anti-leishmanial, immunomodulatory and anti-oxidative activity of quercetin against cutaneous leishmaniasis caused by Leishmania major. Asian Pac J Trop Biomed. 2023;13(1):26–34.
14. Da Silva ER, Maquiaveli C do C, Magalhães PP. The leishmanicidal flavonols quercetin and quercitrin target Leishmania (Leishmania) amazonensis arginase. Exp Parasitol. 2012;130(3):183–8.
15. Fonseca-Silva F, Inacio JDF, Canto-Cavalheiro MM, et al. Reactive oxygen species production by quercetin causes the death of Leishmania amazonensis intracellular amastigotes. J Nat Prod. 2013;76(8):1505–8.
16. Mehwish S, Varikuti S, Ali Khan M, et al. Bioflavonoid-Induced Apoptosis and DNA Damage in Amastigotes and Promastigotes of Leishmania donovani: Deciphering the Mode of Action. Molecules. 2021;26(19):5843.
17. AbouLaila M, Abdelaziz A, Rizk M, et al. Evaluation of the in vitro and in vivo inhibitory effects of quercetin on the growth of Babesia and Theileria parasites. Damanhour J Vet Sci. 2019;2(1):23–7.
18. Khalid SA, Farouk A, Geary TG, et al. Potential antimalarial candidates from African plants: and in vitro approach using Plasmodium falciparum. J Ethnopharmacol. 1986;15(2):201–9.
19. Freitas RF, Prokopczyk IM, Zottis A, et al. Discovery of novel Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase inhibitors. Bioorg Med Chem. 2009; 17(6):2476–82.
20. Tasdemir D, Kaiser M, Brun R, et al. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob Agents Chemother. 2006;50(4):1352–64.
21. Mohebali F, Aghabarari B, Vaezi MR, et al. Biomacromolecule chitosan carrying meglumine antimoniate coated on a silver/polyurethane nanostructure as a wound dressing: Therapeutic efficacy on cutaneous leishmaniasis caused by Leishmania major in BALB/c mice. Int J Biol Macromol. 2025;307(Pt 2).
22. Tavakoli P, Ghaffarifar F, Delavari H, et al. Synthesis of Tellurium Oxide (TeO2) Nanorods and Nanoflakes and Evaluation of Its Efficacy Against Leishmania major In vitro and In vivo. Acta Parasitol. 2022;67(1):143–52.
23. Ghaffari AD, Barati M, KarimiPourSaryazdi A, et al. In vitro and in vivo study on antiprotozoal activity of calcium oxide (CaO) and magnesium oxide (MgO) nanoparticles on promastigote and amastigote forms of Leishmania major. Acta Trop. 2023;238 :106788.
24. Saleh F, Kheirandish F, Abbasi M, et al. Comparison of biosynthetic zinc oxide nanoparticle and glucantime cytotoxic effects on Leishmania major (MRHO/IR/75/ER). J Basic Microbiol. 2024;64(5): e2300490.
25. Rahnama V, Motazedian M, Mohammadi-Samani S, et al. Artemether-loaded nanostructured lipid carriers: preparation, characterization, and evaluation of in vitro effect on Leishmania major. Res Pharm Sci. 2021;16(6):623–33.
26. Abazari R, Mahjoub AR, Molaie S, et al. The effect of different parameters under ultrasound irradiation for synthesis of new nanostructured Fe3O4@bio-MOF as an efficient anti-leishmanial in vitro and in vivo conditions. Ultrason Sonochem. 2018;43:248–61.
27. Saryazdi KA, Dalimi A, Sadeghi SH, et al. Effects of silver nanoparticle based on ginger extract on Leishmania infantum and Leishmania tropica parasites: in vitro. Arch Razi Inst. 2024;79(2):335.
28. Chaurasia M, Singh PK, Jaiswal AK, et al. Bioinspired Calcium Phosphate Nanoparticles Featuring as Efficient Carrier and Prompter for Macrophage Intervention in Experimental Leishmaniasis. Pharm Res. 2016;33(11):2617–29.
29. Allahverdiyev AM, Abamor ES, Bagirova M, et al. Antileishmanial effect of silver nanoparticles and their enhanced antiparasitic activity under ultraviolet light. Int J Nanomedicine. 2011;6:2705–14.
30. Rodrigues JM, Croft SL, Fessi H, et al. The activity and ultrastructural localization of primaquine-loaded poly (d,l-lactide) nanoparticles in Leishmania donovani infected mice. Trop Med Parasitol. 1994;45(3):223–8.
31. Özel Y, Çavuş I, Yilmaz U, et al. (Investigation of Cytotoxic and Antileishmanial Activity of Hybrid Silver Nanoparticle Complexes: Potential Drug Candidates against Leishmania Species). Mikrobiyol Bul. 2024 (2):182-195.
32. Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84–9.
33. Leopoldini M, Russo N, Chiodo S, et al. Iron chelation by the powerful antioxidant flavonoid quercetin. J Agric Food Chem. 2006;54(17):6343–51.
34. Elizondo-Luévano JH, Pérez-Narváez OA, Sánchez-García E, et al. In-Vitro Effect of Kalanchoe daigremontiana and Its Main Component, Quercetin against Entamoeba histolytica and Trichomonas vaginalis. Iran J Parasitol. 2021;16(3):394–401.
35. Guo Y, Bruno RS. Endogenous and exogenous mediators of quercetin bioavailability. J Nutr Biochem. 2015;26(3):201–10.
36. Riva A, Ronchi M, Petrangolini G, et al. Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin. Eur J Drug Metab Pharmacokinet. 2019;44(2):169-177.
37. Omi N, Shiba H, Nishimura E, et al. Effects of enzymatically modified isoquercitrin in supplementary protein powder on athlete body composition: A randomized, placebo-controlled, double-blind trial. J Int Soc Sports Nutr. 2019;16(1):39.
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| Issue | Vol 21 No 2 (2026) | |
| Section | Original Article(s) | |
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| L. major Quercetin ZnMgFe₂O₄ Nanoparticle In vitro | ||
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How to Cite
1.
Gheisari S, Delavari M, Salimikia I, Sobhani Nasab A. Antileishmanial Activity of Quercetin-ZnMgFe2O4 Nanostructure on Leishmania major in Vitro. Iran J Parasitol. 2026;21(2):217-226.
