Royal Jelly Ameliorates Behavioral Deficits, Cholinergic System Deficiency, and Autonomic Nervous Dysfunction in Ovariectomized Cholesterol-Fed Rabbits.

Yongming Pan,Mengmeng You,Keyan Zhu,Minli Chen,Fuliang Hu,Ping Jin,Jianqin Xu,Qinqin Yang

doi:10.3390/molecules24061149

Yongming Pan, Mengmeng You + Show 6 more

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https://doi.org/10.3390/molecules24061149

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Abstract

Estrogen deficiency after menopause is associated with autonomic nervous changes, leading to memory impairment and increased susceptibility to Alzheimer’s disease (AD). Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Here, we investigated whether RJ can improve behavior, cholinergic and autonomic nervous function in ovariectomized (OVX) cholesterol-fed rabbits. OVX rabbits on high-cholesterol diet were administered with RJ for 12 weeks. The results showed that RJ could significantly improve the behavioral deficits of OVX cholesterol-fed rabbits and image structure of the brain. RJ reduced body weight, blood lipid, as well as the levels of amyloid-beta (Aβ), acetylcholinesterase (AchE), and malonaldehyde (MDA) in the brain. Moreover, RJ also increased the activities of choline acetyltransferase (ChAT) and superoxide dismutase (SOD) in the brain, and enhanced heart rate variability (HRV) and Baroreflex sensitivity (BRS) in OVX cholesterol-fed rabbits. Furthermore, RJ was also shown to reduce the content of Evans blue and the expression levels of Aβ, beta-site APP cleaving enzyme 1(BACE1), and receptor for advanced glycation end products (RAGE), and increase the expression level of LDL(low density lipoprotein) receptor-related protein 1 (LRP-1) in the brain. Our findings suggested that RJ has beneficial effects in neurological disorders of postmenopausal women, which were associated with reducing cholesterol and Aβ deposition, enhancing the estrogen levels and the activities of cholinergic and antioxidant systems, and ameliorating the blood–brain barrier (BBB) permeability and restoring autonomic nervous system.

Highlights

Decreased estrogen levels after menopause can lead to cognitive dysfunction and increasing the risk of Alzheimer’s disease (AD) [1]
We investigated the protective effects of Royal jelly (RJ) on neurological disorders in ovariectomized (OVX) cholesterol-fed rabbits through behavior, blood biochemistry, autonomic nervous function, blood–brain barrier (BBB) permeability, magnetic resonance imaging (MRI), and pathological detection and analysis, providing experimental evidence for the application of RJ in the prevention of neurological disorders in menopause women
It was found that the levels of Aβ and BACE1 in the brain of Sham and high cholesterol diet (HCD) rabbits with estrogen protection were lower than those of OVX + HCD rabbits, and yet we found that RJ could significantly reduce the body weight, blood lipid, Aβ level as well as the expression of BACE1, thereby inhibiting the production of Aβ in OVX cholesterol-fed rabbit brains, suggesting that estrogen supplementation can inhibit the production of Aβ in early postmenopausal women

Summary

Introduction

Decreased estrogen levels after menopause can lead to cognitive dysfunction and increasing the risk of Alzheimer’s disease (AD) [1]. Animal studies have shown that the loss of ovarian function was associated with altered brain metabolism and increased. The relative susceptibility of women to AD is associated with the loss of menopausal hormones, and with the action of CNS. It was recently found that several central nervous structures mainly affected by AD were involved in the function of autonomic nervous system (ANS), such as cerebral neocortex, insular cortex, brain stem, and hypothalamus, etc. Recent studies have demonstrated that the ANS function in premenopausal women is higher than in postmenopausal women, and estrogen can affect central and peripheral ANS by regulating sympathetic/parasympathetic nerves [7], suggesting that menopause is associated with

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