Tehran University of Medical Sciences Iranian Journal of Parasitology 1735-7020 20 4 2025 12 07 Spirulina platensis as a Natural Antileishmanial Candidate: Effective Inhibition of LRV2+ and LRV2− Leishmania major Isolates In Vitro 553 562 Mahya Allahmoradi Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Homa Hajjaran 1. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2. Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran Zahra Mirabedini Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Hamed Mirjalali Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mehdi Mohebali Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Behnam Mohammadi-Ghalehbin Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran 2025 04 27 2025 12 07 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. https://ijpa.tums.ac.ir/index.php/ijpa/article/view/4582 https://ijpa.tums.ac.ir/index.php/ijpa/article/download/4582/1464