Neuroprotective efficacy of royal jelly and propolis against cadmium-induced dysregulation of neurogenesis and neurotransmitters in the brain of rats: Molecular mechanisms and ultrastructure investigations

Abstract

This study seeks to evaluate the neuroprotective efficacy of royal jelly (RJ) and propolis (P) against cadmium-induced dysregulation of neurogenesis and neurotransmitters in the brains of Wistar male rats and decipher implicated underlying mechanisms. We probed oxidative stress, inflammatory, neurotransmitter, and neurogenesis biomarkers, along with histopathological and ultrastructural attributes. Energy dispersive x-ray (EDX) microanalysis revealed that RJ and P administration diminished the cadmium (Cd) ratio in the brain compared with the Cd-administered rats. Accordingly, Cd triggered a noticeable disturbance in recognition, which was counterbalanced by RJ and P therapies. Additionally, Cd-administered rats demonstrated lessened superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) activities with increased malondialdehyde (MDA) level. Furthermore, Cd treatment led to substantial rises in nuclear factor kappa B (NF-κB), Indoleamine 2,3-dioxygenase (IDO), and tumor necrosis factor alpha (TNF-α) concentrations, with a dwindled tissue inhibitor of metalloproteinase 3 (TIMP3) level. These deregulations were significantly rectified by RJ and P therapies. Crucially, Cd accumulation disrupted levels of neurotransmitters, including dopamine (DA), serotonin (SRO), and amyloid beta 1–42 (Aβ1–42), and acetylcholinesterase (AChE) activity, along with a notable diminution in neurogenesis biomarkers, involving brain-derived neurotrophic factor (BDNF) level and doublecortin (DCX) mRNA expression. Notably, RJ and P counteracted these interferences and reinstated levels of major factors to those in the control group. Interestingly, glial fibrillary acidic protein (GFAP) immunohistochemistry, histological, and ultrastructure investigations disclosed salient correlations with biochemical findings. Altogether, our results substantiate the effective and better utilization of RJ than P to counterbalance the pernicious Cd consequences.