RT Journal Article SR Electronic(1) A1 Sharifi, Fatemeh A1 Sharififar, Fariba A1 Pournamdari, Mostafa A1 Ansari, Mehdi A1 Tavakoli Oliaee, Razieh A1 Bamorovat, Mehdi A1 Khosravi, Ahmad A1 Keyhani, Ali Reza A1 Salarkia, Ehsan A1 Mortazaeizdeh, Abbas A1 Dabiri, Shahriar A1 Khamesipour, Ali A1 Sharifi, IrajYR 2021 T1 Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile JF Journal of Medical Microbiology, VO 70 IS 6 OP SP 001333 DO https://doi.org/10.1099/jmm.0.001333 PB Microbiology Society, SN 1473-5644, AB Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species. Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development. Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action. Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure. Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major. Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings., UL https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.001333