Propolis Ameliorates Alcohol-Induced Depressive Symptoms in C57BL/6J Mice by Regulating Intestinal Mucosal Barrier Function and Inflammatory Reaction

Abstract

Accumulating evidence points to a critical role of the brain gut axis as an important para-digm for many central nervous system diseases. Recent studies suggest that propolis has obvious neuroprotective properties and functionality in regulating intestinal bacteria flora, hinting at a potential key effect at both terminals of this axis regulation. However, currently no clear evidence confirms the effects of propolis on alcohol-induced depression. Here, we establish an alcoholic depression model with C57BL/6J mice and demonstrate that treatment with propolis protects against alcohol-induced depressive symptoms by behavioral tests. In addition, propolis attenuates the in-jury of nerve cells in the hippocampal region and restores the serum levels of brain-derived neu-rotrophic factor (BDNF) and dopamine (DA) in mice with alcohol-induced depression. Pathology and biotin tracer assays show that propolis repairs the intestinal leakage caused by alcohol. Addi-tionally, propolis treatment increases the expression levels of intestinal intercellular tight junctions’ (TJs’) structural proteins Claudin-1, Occludin and zona occludens-1 (ZO-1), as well as the activation state of the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) signaling pathway, which is closely related to the intestinal permeability. Furthermore, propolis can reduce the levels of pro-inflammatory, lipopolysaccharide (LPS) and fatty-acid-binding protein 2 (FABP2), suggesting the significance of the inflammatory response in alcoholic depression. Collectively, our findings indi-cate that propolis exerted an improving effect on alcohol-induced depressive symptoms by amelio-rating brain gut dysfunction.