Tehran University of Medical Sciences Journal of Arthropod-Borne Diseases 2322-1984 0 0 2026 04 12 1911 1911 Razieh Moghimian Department of Biology and Control of Disease Vectors, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran Mehdi Mohebali Center for Research of Endemic Parasites of Iran (CREPI), Tehran University of Medical Sciences, Tehran, Iran Hamid Reza Basseri Department of Biology and Control of Disease Vectors, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Behnaz Akhoundi Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Ehsan Salarkia Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran Abbas Aghaei Afshar Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran Kamran Akbarzadeh Department of Biology and Control of Disease Vectors, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2026 01 24 2026 04 09 Background: Cutaneous leishmaniasis (CL) is a neglected tropical disease with limited therapeutic options due to drug resistance, systemic toxicity, and prolonged treatment duration associated with pentavalent antimonials such as meglu­mine antimoniate (MAT). Lucilia sericata larvae produce hemolymph containing bioactive compounds with antimicro­bial and immunomodulatory properties, suggesting potential as an alternative or adjunct therapy for CL. Methods: Hemolymph was extracted from sterile third-instar L. sericata larvae and characterized using SDS-PAGE and Fast Protein Liquid Chromatography. The antileishmanial activity of whole hemolymph, its most active fraction, MAT, and their combinations was assessed against promastigote and amastigote forms of L. major. Cytotoxicity, cyto­kine gene expression and reactive oxygen species production were evaluated. In vivo efficacy was examined in BALB/c mice infected with L. major and treated for 28 days with topical hemolymph cream, intramuscular MAT, or combina­tion therapy. Lesion size and parasite burden were measured. Results: Whole hemolymph and the active fraction significantly inhibited parasite growth in vitro, while combination treatments showed strong synergistic effects. Treatments enhanced Th1-associated cytokines, suppressed Th2 cytokines, and increased reactive oxygen species production. In vivo, hemolymph cream reduced lesion size and parasite load, with the greatest improvement observed in the combination group. No significant cytotoxicity was detected. Conclusions: Lucilia sericata larval hemolymph exhibits potent antileishmanial and immunomodulatory activity and rep­resents a promising and safe topical therapy for CL. Combination with MAT enhances efficacy and may reduce sys­temic toxicity. https://jad.tums.ac.ir/index.php/jad/article/view/1911 https://jad.tums.ac.ir/index.php/jad/article/download/1911/717 https://jad.tums.ac.ir/index.php/jad/article/download/1911/718