Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Abstract

The astronomical increase of the world’s aged population is associated with the increased prevalence of neurodegenerative diseases, heightened disability, and extremely high costs of care. Alzheimer’s Disease (AD) is a widespread, age-related, multifactorial neurodegenerative disease that has enormous social and financial drawbacks worldwide. The unsatisfactory outcomes of available AD pharmacotherapy necessitate the search for alternative natural resources that can target various the underlying mechanisms of AD pathology and reduce disease occurrence and/or progression. Royal jelly (RJ) is the main food of bee queens; it contributes to their fertility, long lifespan, and memory performance. It represents a potent nutraceutical with various pharmacological properties, and has been used in a number of preclinical studies to target AD and age-related cognitive deterioration. To understand the mechanisms through which RJ affects cognitive performance both in natural aging and AD, we reviewed the literature, elaborating on the metabolic, molecular, and cellular mechanisms that mediate its anti-AD effects. Preclinical findings revealed that RJ acts as a multidomain cognitive enhancer that can restore cognitive performance in aged and AD models. It promotes brain cell survival and function by targeting multiple adversities in the neuronal microenvironment such as inflammation, oxidative stress, mitochondrial alterations, impaired proteostasis, amyloid-β toxicity, Ca excitotoxicity, and bioenergetic challenges. Human trials using RJ in AD are limited in quantity and quality. Here, the limitations of RJ-based treatment strategies are discussed, and directions for future studies examining the effect of RJ in cognitively impaired subjects are noted.

Intermittent Fasting, Dietary Modifications, and Exercise for the Control of Gestational Diabetes and Maternal Mood Dysregulation: A Review and a Case Report

“…PL also inhibits the production of proapoptotic molecules in the endoplasmic reticulum (ER) stress pathway that are evoked by chronic ER stress resulting in increased human β-cell survival and decreased incidence of diabetes in rodents [ 53 ]. However, alterations in PL develop in obesity where vital metabolic molecules become dysregulated, such as adiponectin, an adipose tissue-derived adipokine that contributes to insulin sensitivity and regulates glucose metabolism [ 54 ]. Because of hypoadiponectinemia, which is often associated with chronic low-grade inflammation [ 54 , 55 ], PL fails to promote β-cell proliferation [ 52 ].…”

“…However, alterations in PL develop in obesity where vital metabolic molecules become dysregulated, such as adiponectin, an adipose tissue-derived adipokine that contributes to insulin sensitivity and regulates glucose metabolism [ 54 ]. Because of hypoadiponectinemia, which is often associated with chronic low-grade inflammation [ 54 , 55 ], PL fails to promote β-cell proliferation [ 52 ]. Instead, it exerts a lipolytic activity—increasing circulating fatty acids—resulting in a maternal metabolism shift toward lipids rather than glucose as a source of energy [ 7 ].…”

“…Gut microbiome imbalance has been recently well-acknowledged as a key contributor to serious disorders including diabetes mellitus and obesity [ 48 , 55 , 57 ], cancer, and a trail of neurodegenerative diseases such as major depression [ 39 , 46 , 58 ], Alzheimer disease [ 54 ], and Parkinson disease [ 59 ]. Many factors interfere with the structure of the gut microbiome either by limiting the diversity of intestinal microflora or by promoting the propagation of endotoxic bacterial species.…”

“…Both depression and diabetes are inflammatory disorders. Research confirms that intense activation of nod-like receptor family pyrin domain containing 3 (NLRP3) and its upstream P2X7 receptors is associated with excessive release of inflammatory mediators (e.g., interleukin (IL)-1β and IL-6) [ 54 , 77 ]. The brain is one of the body organs that are affected by inflammatory reactions that follow feminine hormonal changes and hyperglycemia that occur during pregnancy.…”

“…The brain is one of the body organs that are affected by inflammatory reactions that follow feminine hormonal changes and hyperglycemia that occur during pregnancy. Such high release of cytokines may damage both neuronal and non-neuronal cells of the brain, which may promote the development of MDs and cognitive changes [ 28 , 54 , 77 ].…”