Royal Jelly Mitigates Cognitive Decline and Anxiety in Female Mice: A Promising Natural Neuroprotective Solution for Alzheimer’s Disease

Background: The incidence of dementia, especially Alzheimer’s disease (AD), is rising, with over 55 million affected globally. Therefore, this disease, for which there is no adequate treatment, is more frequent and prevalent in women. Royal jelly, a bee secretion, is known for its health benefits and contains proteins, carbohydrates, lipids, minerals, polyphenols, enzymes, and B vitamins, as well as anti-inflammatory and antioxidant properties relevant to AD. Thus, we aimed to investigate the chemical compounds in royal jelly extract and their effect on neurobehavioral changes in an AD female model. Methods: In vitro studies were used to investigate the chemical and physicochemical properties of the royal jelly extract. In vivo studies, we divided female mice into five groups (n = 25): Control (C), Alzheimer (ALZ), ALZ standard (ALZ-STD, rivastigmine 1 mg/Kg), ALZ-D1 (royal jelly 150 mg/kg), and ALZ-D2 (royal jelly 300 mg/kg). The mice received the treatments orally at 45 days. We induced the AD model by orally administering aluminum chloride at 100 mg/kg and intraperitoneally injecting D-galactose at 120 mg/kg for 45 consecutive days, after which we subjected the animals to the radial arm maze, Morris water maze, elevated plus maze, and forced swim tests. Results: Analyses showed moderate acidity and a rich bioactive profile, with flavonoids being more prevalent. Antioxidant activity tests indicated moderate efficacy, while FTIR-ATR analysis revealed the chemical complexity of royal jelly. The royal jelly extract used in the study did not induce toxicity in vivo. Notably, royal jelly improved cognitive deficits, neurodegeneration, and reduced anxiety in AD. Conclusions: The study suggests that royal jelly extract has promising neuroprotective properties and could be a viable natural therapeutic option for AD.