Protective Effects of Murrayafoline A Against Heat-Induced Male Infertility in Drosophila melanogaster: In Vivo...

Male infertility, often caused by disruptions in spermatogenesis-the differentiation of diploid germline stem cells into mature spermatozoa-is a global concern. Vasa, a DEAD-box RNA helicase, plays a crucial role in this process, particularly in Drosophila melanogaster, where it regulates mRNA translation essential for germline development. Murrayafoline A (MurA), a carbazole alkaloid from Glycosmis stenocarpa, shows therapeutic potential for the treatment of various diseases. Therefore, this study aims to investigate the protective effects of MurA against heat-induced male infertility in Drosophila in vivo assays and computational simulations. Heat stress significantly reduced egg-hatching rates and impaired spermatogonia integrity, while MurA supplementation strongly improved these outcomes. Molecular docking revealed that MurA binds strongly to Vasa within the ATP-binding pocket, forming hydrogen bonds and hydrophobic interactions with a binding affinity of -8.67 kcal/mol. Molecular dynamics simulations confirmed stable Vasa-MurA interactions over 100 ns, with conserved residues and hydrophobic contacts stabilizing the complex. These findings, supported by in vivo rescue of fertility and germline integrity together with computational simulations, suggest a plausible mechanism of action for MurA that warrants further experimental investigation.