Thioctic acid shield against lipopolysaccharide depression and endoplasmic reticulum stress: GR7M/Homer/ATF6 signaling

<b>Aim:</b> Endoplasmic reticulum stress triggers neuronal unfolded protein accumulation, contributing to the pathophysiology of depression psychiatric illnesses.<b>Materials & methods:</b> The brain-derived neurotrophic factor (<i>BDNF</i>), metabotropic glutamate receptor type 7 (<i>GRM7</i>), phosphoinisitol kinase-3 (<i>PIK3</i>), serine/threonine kinase 1 (<i>AKT</i>) and <i>Homer1</i> may afford an important signaling pathways in LPS induced depression rat model. Herein, thioctic acid, Burdock and propolis therapeutic index on lipopolysaccharide (LPS)-induced depression was monitored. <i>BDNF/PI3K/GR7M/ATF6/CHOP/XBP/AKT/Homer-1</i> signaling pathways also opened a novel avenue in the integration of synaptic neurotransmission.<b>Results:</b> The aforementioned treatments elevated GR7M/BDNF/GABA gene expression meanwhile decreased reactive oxygen species generation (Malondialdehyde/glutathione reductase/Total antioxidant capacity) and reduced the expression of <i>ATF6/CHOP/PI3K/AKT/XBP/Homer-1</i> post LPS elevation.<b>Conclusion:</b> Thioctic acid, propolis and Burdock are prospective therapeutic agents via <i>GRM7/BDNF/AKT/PI3K/ATF6/XBP/homer</i> -<i>1</i> signaling pathways in LPS-induced depression.