Neuroregulatory effect of royal jelly

Royal jelly (RJ), a nutrient-rich secretion fed exclusively to queen honeybees, exhibits diverse biological activities. Due to limited insights into its effects on central nervous system (CNS)-related functions and pathologies, this review attempts to recapitalize the recent advances of neuroregulatory function of RJ in mammals and humans. Another central aim of this review is to summarize the known mechanisms underlying the neuroregulatory effect of RJ. RJ components were first discussed concerning their link to neuroprotection, with a focus on the queen bee acid (QBA, 10-HDA, trans-10‑hydroxy-2-decenoic acid), MRJPs (major royal jelly proteins), and microbiota. The neuroregulatory implications of RJ are then categorized into three domains: fundamental CNS functions, including learning and memory, in vitro neuronal cell activity and social behavior; neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), anxiety and depression; neurotoxic events. In terms of mechanistic insights, RJ modulates neuroinflammation, a pivotal driver of neurological disorders, and acts as an HDAC (histone deacetylase) inhibitor among other epigenetic regulators, influencing gene expression in the CNS. Emerging evidence also implicates the microbiota-gut-brain (MGB) axis, where RJ alters gut microbiota composition, subsequently impacting brain function. Finally, we outline critical research directions, including clinical significance, comparisons with other honeybee products, epigenetic mechanisms, and RJ's untapped role in reshaping social behaviors. This review aims to consolidate our knowledge on the neuroregulatory effects of RJ, underscoring its therapeutic potential for neurological conditions in both nutritional and pharmaceutical contexts.