Background Honeybees are one of the most important pollinators in the world, and their products are nowadays included in most anticancer, antiallergic, antimicrobial drugs and are included in cosmetic treatments. In the present study, honeybee venom and Egyptian ethanolic propolis extract (EP) were focused to test their effect on health and some genes for honeybee workers (defensin2, abaecin, hymenoptaecin, vitellogenin, and juvenile hormone esterase). Results Honeybee venom and Egyptian

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... s extract (EP) were used as supplements in the nutrition with different concentrations in Varroa mites-infected colonies to measure the colonies' activities after treatment. The immune-related genes and antimicrobial peptides (AMPs) were evaluated by using qRT-PCR. Treated colonies with HBV and EP showed up-regulation of immune and immune-related genes' expressions and increased the life span, activities and their density of bee workers. The data illustrated that the highest gene expression fold of juvenile hormone esterase was detected in the treated colonies with Egyptian ethanolic propolis extract (EP), while the highest vitellogenin expression fold in treated colonies was with honeybee venom. The up-regulation of antimicrobial peptides occurred in colonies with both treatments. Conclusion The findings suggest that honeybee venom and Egyptian ethanolic propolis extract (EP) could be used as potential supplements, even at the lowest concentration to develop the immunity of worker bees to increase their efficiency and prevent loss of honeybee colonies due to several diseases closely associated with Varroa mites' infections that cause sudden death.