Royal Jelly Alleviates Cognitive Deficits and β-Amyloid Accumulation in APP/PS1 Mouse Model Via Activation of the cAMP/PKA/CREB/BDNF Pathway and Inhibition of Neuronal Apoptosis

Abstract

Alzheimer’s disease (AD) is characterized clinically by progressive cognitive decline and pathologically by the accumulation of amyloid-β (Aβ) in the brain. Royal jelly (RJ), a secretion of honeybee hypopharyngeal and mandibular glands, has previously been shown to have anti-aging and neuromodulatory activities. In this study, we discovered that 3 months of RJ treatment substantially ameliorated behavioral deficits of APP/PS1 mice in the Morris Water Maze (MWM) test and step-down passive avoidance test. Our data also showed that RJ significantly diminished amyloid plaque pathology in APP/PS1 mice. Furthermore, RJ alleviated c-Jun N-terminal kinase (JNK) phosphorylation-induced neuronal apoptosis by suppressing oxidative stress. Importantly, hippocampal cyclic adenosine monophosphate (cAMP), p-PKA, p-CREB and BDNF levels were significantly increased in the APP/PS1 mice after RJ treatment, indicating that the cAMP/PKA/CREB/BDNF pathway might be related to the ameliorative effect of RJ on cognitive decline. Collectively, these results provide a scientific basis for using RJ as a functional food for targeting AD pathology.

Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

“…More, PD is known as manifest Lewy body dementia because severe cognitive alterations develop, especially during late stages of the disease [ 19 ]. Research shows that propolis and RJ possess a capacity to improve cognitive performance [ 71 ] and alleviate depressive symptoms through mitigation of oxidative stress [ 117 ] and activation of signaling pathways that promote the production of various neurotrophic factors such as BDNF [ 118 ], GDNF [ 102 ], and NGF [ 119 , 120 ]. Altogether, according to these scenarios, propolis and RJ may represent a multidimensional treatment, which may promote the quality of life among PD patients.…”

Tau inhibits PKA by nuclear proteasome‐dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation

“…Here, we observed that overexpression of hTau in hippocampal neurons pronouncedly impaired PKA signaling in both total lysates and the nuclear fraction compared with the vector control. The role of PKA on memory maintenance in different brain subset and pathologies is not always consistent, some researchers show that Aβ inhibits PKA, while activating PKA in hippocampus can improve cognitive functions (Gong et al, ; You et al, ). Other studies show that PKA accelerates tau phosphorylation, while inhibiting PKA in the prefrontal cortex improves memory in both aged rats and monkeys (Wang et al, ; Xie et al, ).…”

New Insights into the Biological and Pharmaceutical Properties of Royal Jelly

“…Memory impairment and depression-like behaviors in ovariectomized rats are recovered to the levels of sham-operated rats by RJ administration [171]. RJ administration has the potential to consolidate the learning, memory abilities, and longevity of honeybees [112], and the intake of RJ has the potential to ameliorate cognitive deficits [103]. RJ ingestion is effective on neurological disorders, such as Alzheimer's disease in postmenopausal patients, via decreasing cholesterol and amyloid-beta deposition, increasing cholinergic response, estrogen level, and also improving the blood-brain barrier and autonomic nervous systems [102].…”