Spirulina platensis as a Natural Antileishmanial Candidate: Effective Inhibition of LRV2+ and LRV2− Leishmania major Isolates In Vitro
-
Mahya Allahmoradi
,
Homa Hajjaran
,
Zahra Mirabedini
,
Hamed Mirjalali
,
Mehdi Mohebali
,
Behnam Mohammadi-Ghalehbin
Abstract
Background: Drug resistance and treatment failure in Leishmania infections are major concerns. Leishmania RNA virus 2 (LRV2) enhances host inflammation, indirectly favoring the parasite. Thus, alternative treatments are needed. Spirulina platensis has shown antimicrobial potential.
Methods: The alcoholic extract of S. platensis was tested against L. major with or without LRV2. Anti-promastigote activity was evaluated directly on parasites, cytotoxicity on J774.A1 macrophages, and anti-amastigote effects using the MTT assay.
Results: The extract showed significant, dose-dependent anti-leishmanial activity against both LRV2+ and LRV2− promastigotes (IC₅₀ = 62.5 μg/mL). J774.A1 cells remained viable at 62.5–2000 μg/mL (P = 0.0005). Amastigote growth was inhibited at 1000 and 2000 μg/mL in both strains.
Conclusion: S. platensis extract exhibits strong anti-leishmanial activity and low cytotoxicity, suggesting its potential as a natural therapeutic candidate against L. major, irrespective of LRV2 status. Further in vivo studies are warranted.
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2. World Health Organization. Leishman-iasis. Fact sheet. 12 January 2023. Avail-able from: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis
3. Mahmoudvand H, Ezzatkhah F, Shari-fifar F, et al. Antileishmanial and cyto-toxic effects of essential oil and meth-anolic extract of Myrtus communis L. Ko-rean J Parasitol. 2015;53(1):21-7.
4. Firooz A, Mortazavi H, Khamesipour A, et al. Old world cutaneous leishmaniasis in Iran: clinical variants and treatments. J Dermatolog Treat. 2021;32(7):673–683.
5. Mabbott NA. The influence of parasite infections on host immunity to co-infection with other pathogens. Front Immunol. 2018;9:411219.
6. Bamorovat M, Sharifi I, Dabiri S, et al. Major risk factors and histopathological profile of treatment failure, relapse and chronic patients with anthroponotic cu-taneous leishmaniasis: A prospective case-control study on treatment out-come and their medical importance. PLoS Negl Trop Dis. 2021;15(1):e0009089.
7. Hadighi R, Mohebali M, Boucher P, et al. Unresponsiveness to Glucantime treatment in Iranian cutaneous leish-maniasis due to drug-resistant Leishma-nia tropica parasites. PLoS Med. 2006;3(5):e162.
8. Croft S, Olliaro P. Leishmaniasis chem-otherapy—challenges and opportuni-ties. Clin Microbiol Infect. 2011;17(10):1478–83.
9. Mesa LE, Vasquez D, Lutgen P, et al. In vitro and in vivo antileishmanial activi-ty of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmani-asis in humans. Rev Soc Bras Med Trop. 2017;50(1):52–60.
10. Zadeh Mehrizi T, Pirali Hamedani M, et al. Effective materials of medicinal plants for Leishmania treatment in vivo environment. J Med Plants. 2020;19(74):39–62.
11. Juszkiewicz A, Basta P, Petriczko E, et al. An attempt to induce an immuno-modulatory effect in rowers with spir-ulina extract. J Int Soc Sports Nutr. 2018;15:9.
12. Mao T, Van de Water J, Gershwin M. Spirulina effects on cytokines. J Med Food. 2000;3(3):135–40.
13. Gershwin ME, Belay A. Spirulina in hu-man nutrition. CRC Press; 2007.
14. Al-ghanayem AA. Antimicrobial activity of Spirulina platensis extracts against cer-tain pathogenic bacteria and fungi. Adv Bioresearch. 2017;8(6):96-101.
15. Mazloomi SM, Samadi M, Davarpanah H, et al. The effect of Spirulina sauce, as a functional food, on cardiometabolic risk factors, oxidative stress biomarkers, glycemic profile, and liver enzymes in nonalcoholic fatty liver disease patients: A randomized double‐blinded clinical trial. Food Sci Nutr. 2022;10(2):317–328.
16. Abd El-Ghany AM, Salama A, Abd El-Ghany NM, et al. New Approach for Controlling Snail Host of Schistosoma mansoni, Biomphalaria alexandrina with Cyanobacterial Strains-Derived C-Phycocyanin. Vector Borne Zoonotic Dis. 2018;18(9):464–468.
17. Lohvina H, Sándor M, Wink M. Effect of Ethanol Solvents on Total Phenolic Content and Antioxidant Properties of Seed Extracts of Fenugreek (Trigonella foe-num-graecum L.) Varieties and Determi-nation of Phenolic Composition by HPLC-ESI-MS. Diversity. 2022;14(1):7.
18. Atayoglu AT, Sözeri Atik D, Bölük E, et al. Evaluating bioactivity and bioacces-sibility properties of the propolis ex-tract prepared with l-lactic acid: An al-ternative solvent to ethanol for propolis extraction. Food Bioscience. 2023;53:102756.
19. Chin C-Y, Jalil J, Ng PY, Ng S-F. Devel-opment and formulation of Moringa oleifera standardised leaf extract film dressing for wound healing application. Journal of ethnopharmacology. J Eth-nopharmacol. 2018;212:188–199.
20. Hajjaran H, Mahdi M, Mohebali M, et al. Detection and molecular identifica-tion of Leishmania RNA virus (LRV) in Iranian Leishmania species. Arch Virol. 2016; 161:3385–3390.
21. Pinto JG, Soares CP. Assessment of Leishmania major and Leishmania braziliensis promastigote viability after photodynamic treatment with alumi-num phthalocyanine tetrasulfonate (AlPcS4). J Venom Anim Toxins Incl Trop Dis. 2011; 17:300–7.
22. Maryati M, Saifudin A, Wahyuni S, et al. Cytotoxic effect of Spirulina platensis ex-tract and Ulva compressa Linn. on cancer cell lines. Food Research. 2020;4(4):1018–1023.
23. Mohammad Rahimi H, Khosravi M, Hesari Z, et al. Anti-Toxoplasma activity and chemical compositions of aquatic extract of Mentha pulegium L. and Rubus idaeus L.: An in vitro study. Food Sci Nutr. 2020;8(7):3656–64.
24. Nemati S, Mohammad Rahimi H, et al. Formulation of Neem oil-loaded solid lipid nanoparticles and evaluation of its anti-Toxoplasma activity. BMC Comple-ment Med Ther. 2022;22(1):122.
25. Koutsoni OS, Karampetsou K, Dotsika E. In vitro screening of antileishmanial activity of natural product compounds: Determination of IC50, CC50 and SI values. Bio Protoc. 2019;9(21): e3410.
26. Mohammad Rahimi H, Hesari Z, Mirsamadi ES, et al. Anti-Toxoplasma gondii activity of rose hip oil-solid lipid nanoparticles. Food Sci Nutr. 2024;12(5):3725–3734.
27. Silva MROd, da Silva GM, Silva ALd, et al. Bioactive compounds of Arthrospira spp. (Spirulina) with potential anticancer activities: a systematic review. ACS Chem Biol. 2021;16(11):2057–2067.
28. Marková I, Koníčková R, Vaňková K, et al. Anti‐angiogenic effects of the blue‐green alga Arthrospira platensis on pancreatic cancer. J Cell Mol Med. 2020;24(4):2402–2415.
29. Scardina T, Fawcett AJ, Patel SJ. Am-photericin-associated infusion-related reactions: a narrative review of pre-medications. Clin Ther. 2021;43(10):1689–1704.
30. Stuart KD, Weeks R, Guilbride L, et al. Molecular organization of Leishmania RNA virus 1. Proceedings of the Na-tional Academy of Sciences. Proc Natl Acad Sci U S A. 1992;89(18):8596–600.
31. Hirahashi T, Matsumoto M, Hazeki K, et al. Activation of the human innate im-mune system by Spirulina: augmentation of interferon production and NK cyto-toxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol. 2002;2(4):423–34.
32. Wu X, Liu Z, Liu Y, et al. Immunostimu-latory effects of polysaccharides from Spirulina platensis in vivo and vitro and their activation mechanism on RAW246. 7 macrophages. Mar Drugs. 2020; 18(11):538.
33. Bourreau E, Ginouves M, Prévot G, et al. Presence of Leishmania RNA virus 1 in Leishmania guyanensis increases the risk of first-line treatment failure and symp-tomatic relapse. J Infect Dis. 2016;213(1):105–11.
34. Saberi R, Fakhar M, Hajjaran H, et al. Leishmania RNA virus 2 (LRV2) exacer-bates dermal lesions caused by Leishma-nia major and comparatively unrespon-sive to meglumine antimoniate treat-ment. Exp Parasitol. 2022; 241:108340.
35. Wulandari DA, Sidhartha E, Setyaning-sih I, et al. Evaluation of antiplasmodial properties of a cyanobacterium, Spiruli-na platensis and its mechanism of action. Nat Prod Res. 2018;32(17):2067–2070.
36. Al-Shuwaili AAA, Al Khanaq MN, Mazal WH. Effect of Algae Spirulina Extrac-tion in treatment of intestinal tissues of mice infected with Cryptosporidium spp. J Wasit Sci Med. 2023;16(1):45–61.
37. Moncada-Diaz MJ, Rodríguez-Almonacid CC, Quiceno-Giraldo E, et al. Drug resistance in Leishmania spp. Pathogens. 2024;13(10):835.
38. González M, Alcolea PJ, Álvarez R, et al. New diarylsulfonamide inhibitors of Leishmania infantum amastigotes. Int J Parasitol Drugs Drug Resist. 2021; 16:45–64.
39. Abdellatief SA, Abdel Rahman AN, Abdallah FD. Evaluation of Im-munostimulant activity of Spirulina platensis (Arthrospira platensis) and Sage (Salvia officinalis) in Nile tilapia (Oreochromis niloticus). Zagazig Vet J. 2018;46(1):25–36.
40. Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Micro-biol Rev. 2006;19(1):111–26.
41. Abdel-Moneim A-ME, El-Saadony MT, Shehata AM, et al. Antioxidant and an-timicrobial activities of Spirulina platensis extracts and biogenic selenium nano-particles against selected pathogenic bacteria and fungi. Saudi J Biol Sci. 2022;29(2):1197–1209.
2. World Health Organization. Leishman-iasis. Fact sheet. 12 January 2023. Avail-able from: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis
3. Mahmoudvand H, Ezzatkhah F, Shari-fifar F, et al. Antileishmanial and cyto-toxic effects of essential oil and meth-anolic extract of Myrtus communis L. Ko-rean J Parasitol. 2015;53(1):21-7.
4. Firooz A, Mortazavi H, Khamesipour A, et al. Old world cutaneous leishmaniasis in Iran: clinical variants and treatments. J Dermatolog Treat. 2021;32(7):673–683.
5. Mabbott NA. The influence of parasite infections on host immunity to co-infection with other pathogens. Front Immunol. 2018;9:411219.
6. Bamorovat M, Sharifi I, Dabiri S, et al. Major risk factors and histopathological profile of treatment failure, relapse and chronic patients with anthroponotic cu-taneous leishmaniasis: A prospective case-control study on treatment out-come and their medical importance. PLoS Negl Trop Dis. 2021;15(1):e0009089.
7. Hadighi R, Mohebali M, Boucher P, et al. Unresponsiveness to Glucantime treatment in Iranian cutaneous leish-maniasis due to drug-resistant Leishma-nia tropica parasites. PLoS Med. 2006;3(5):e162.
8. Croft S, Olliaro P. Leishmaniasis chem-otherapy—challenges and opportuni-ties. Clin Microbiol Infect. 2011;17(10):1478–83.
9. Mesa LE, Vasquez D, Lutgen P, et al. In vitro and in vivo antileishmanial activi-ty of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmani-asis in humans. Rev Soc Bras Med Trop. 2017;50(1):52–60.
10. Zadeh Mehrizi T, Pirali Hamedani M, et al. Effective materials of medicinal plants for Leishmania treatment in vivo environment. J Med Plants. 2020;19(74):39–62.
11. Juszkiewicz A, Basta P, Petriczko E, et al. An attempt to induce an immuno-modulatory effect in rowers with spir-ulina extract. J Int Soc Sports Nutr. 2018;15:9.
12. Mao T, Van de Water J, Gershwin M. Spirulina effects on cytokines. J Med Food. 2000;3(3):135–40.
13. Gershwin ME, Belay A. Spirulina in hu-man nutrition. CRC Press; 2007.
14. Al-ghanayem AA. Antimicrobial activity of Spirulina platensis extracts against cer-tain pathogenic bacteria and fungi. Adv Bioresearch. 2017;8(6):96-101.
15. Mazloomi SM, Samadi M, Davarpanah H, et al. The effect of Spirulina sauce, as a functional food, on cardiometabolic risk factors, oxidative stress biomarkers, glycemic profile, and liver enzymes in nonalcoholic fatty liver disease patients: A randomized double‐blinded clinical trial. Food Sci Nutr. 2022;10(2):317–328.
16. Abd El-Ghany AM, Salama A, Abd El-Ghany NM, et al. New Approach for Controlling Snail Host of Schistosoma mansoni, Biomphalaria alexandrina with Cyanobacterial Strains-Derived C-Phycocyanin. Vector Borne Zoonotic Dis. 2018;18(9):464–468.
17. Lohvina H, Sándor M, Wink M. Effect of Ethanol Solvents on Total Phenolic Content and Antioxidant Properties of Seed Extracts of Fenugreek (Trigonella foe-num-graecum L.) Varieties and Determi-nation of Phenolic Composition by HPLC-ESI-MS. Diversity. 2022;14(1):7.
18. Atayoglu AT, Sözeri Atik D, Bölük E, et al. Evaluating bioactivity and bioacces-sibility properties of the propolis ex-tract prepared with l-lactic acid: An al-ternative solvent to ethanol for propolis extraction. Food Bioscience. 2023;53:102756.
19. Chin C-Y, Jalil J, Ng PY, Ng S-F. Devel-opment and formulation of Moringa oleifera standardised leaf extract film dressing for wound healing application. Journal of ethnopharmacology. J Eth-nopharmacol. 2018;212:188–199.
20. Hajjaran H, Mahdi M, Mohebali M, et al. Detection and molecular identifica-tion of Leishmania RNA virus (LRV) in Iranian Leishmania species. Arch Virol. 2016; 161:3385–3390.
21. Pinto JG, Soares CP. Assessment of Leishmania major and Leishmania braziliensis promastigote viability after photodynamic treatment with alumi-num phthalocyanine tetrasulfonate (AlPcS4). J Venom Anim Toxins Incl Trop Dis. 2011; 17:300–7.
22. Maryati M, Saifudin A, Wahyuni S, et al. Cytotoxic effect of Spirulina platensis ex-tract and Ulva compressa Linn. on cancer cell lines. Food Research. 2020;4(4):1018–1023.
23. Mohammad Rahimi H, Khosravi M, Hesari Z, et al. Anti-Toxoplasma activity and chemical compositions of aquatic extract of Mentha pulegium L. and Rubus idaeus L.: An in vitro study. Food Sci Nutr. 2020;8(7):3656–64.
24. Nemati S, Mohammad Rahimi H, et al. Formulation of Neem oil-loaded solid lipid nanoparticles and evaluation of its anti-Toxoplasma activity. BMC Comple-ment Med Ther. 2022;22(1):122.
25. Koutsoni OS, Karampetsou K, Dotsika E. In vitro screening of antileishmanial activity of natural product compounds: Determination of IC50, CC50 and SI values. Bio Protoc. 2019;9(21): e3410.
26. Mohammad Rahimi H, Hesari Z, Mirsamadi ES, et al. Anti-Toxoplasma gondii activity of rose hip oil-solid lipid nanoparticles. Food Sci Nutr. 2024;12(5):3725–3734.
27. Silva MROd, da Silva GM, Silva ALd, et al. Bioactive compounds of Arthrospira spp. (Spirulina) with potential anticancer activities: a systematic review. ACS Chem Biol. 2021;16(11):2057–2067.
28. Marková I, Koníčková R, Vaňková K, et al. Anti‐angiogenic effects of the blue‐green alga Arthrospira platensis on pancreatic cancer. J Cell Mol Med. 2020;24(4):2402–2415.
29. Scardina T, Fawcett AJ, Patel SJ. Am-photericin-associated infusion-related reactions: a narrative review of pre-medications. Clin Ther. 2021;43(10):1689–1704.
30. Stuart KD, Weeks R, Guilbride L, et al. Molecular organization of Leishmania RNA virus 1. Proceedings of the Na-tional Academy of Sciences. Proc Natl Acad Sci U S A. 1992;89(18):8596–600.
31. Hirahashi T, Matsumoto M, Hazeki K, et al. Activation of the human innate im-mune system by Spirulina: augmentation of interferon production and NK cyto-toxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol. 2002;2(4):423–34.
32. Wu X, Liu Z, Liu Y, et al. Immunostimu-latory effects of polysaccharides from Spirulina platensis in vivo and vitro and their activation mechanism on RAW246. 7 macrophages. Mar Drugs. 2020; 18(11):538.
33. Bourreau E, Ginouves M, Prévot G, et al. Presence of Leishmania RNA virus 1 in Leishmania guyanensis increases the risk of first-line treatment failure and symp-tomatic relapse. J Infect Dis. 2016;213(1):105–11.
34. Saberi R, Fakhar M, Hajjaran H, et al. Leishmania RNA virus 2 (LRV2) exacer-bates dermal lesions caused by Leishma-nia major and comparatively unrespon-sive to meglumine antimoniate treat-ment. Exp Parasitol. 2022; 241:108340.
35. Wulandari DA, Sidhartha E, Setyaning-sih I, et al. Evaluation of antiplasmodial properties of a cyanobacterium, Spiruli-na platensis and its mechanism of action. Nat Prod Res. 2018;32(17):2067–2070.
36. Al-Shuwaili AAA, Al Khanaq MN, Mazal WH. Effect of Algae Spirulina Extrac-tion in treatment of intestinal tissues of mice infected with Cryptosporidium spp. J Wasit Sci Med. 2023;16(1):45–61.
37. Moncada-Diaz MJ, Rodríguez-Almonacid CC, Quiceno-Giraldo E, et al. Drug resistance in Leishmania spp. Pathogens. 2024;13(10):835.
38. González M, Alcolea PJ, Álvarez R, et al. New diarylsulfonamide inhibitors of Leishmania infantum amastigotes. Int J Parasitol Drugs Drug Resist. 2021; 16:45–64.
39. Abdellatief SA, Abdel Rahman AN, Abdallah FD. Evaluation of Im-munostimulant activity of Spirulina platensis (Arthrospira platensis) and Sage (Salvia officinalis) in Nile tilapia (Oreochromis niloticus). Zagazig Vet J. 2018;46(1):25–36.
40. Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Micro-biol Rev. 2006;19(1):111–26.
41. Abdel-Moneim A-ME, El-Saadony MT, Shehata AM, et al. Antioxidant and an-timicrobial activities of Spirulina platensis extracts and biogenic selenium nano-particles against selected pathogenic bacteria and fungi. Saudi J Biol Sci. 2022;29(2):1197–1209.
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| Issue | Vol 20 No 4 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v20i4.20463 | |
| Keywords | ||
| Leishmania major Herbal medicine Spirulina platensis (Arthrospira platensis); Leishmania RNA virus 2 | ||
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How to Cite
1.
Allahmoradi M, Hajjaran H, Mirabedini Z, Mirjalali H, Mohebali M, Mohammadi-Ghalehbin B. Spirulina platensis as a Natural Antileishmanial Candidate: Effective Inhibition of LRV2+ and LRV2− Leishmania major Isolates In Vitro. Iran J Parasitol. 2025;20(4):553-562.
