Anti-neuroinflammatory effects of auricularia polytricha extracts on bisphenol a (BPA)-induced microglial cell activation and reduction of hippocampal cell damage

Abstract

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics, it has been reported that BPA can activate neuroinflammation. Neuroinflammation is a brain pathology that involves the high levels of pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α). An excessive TNF-α expression could result in neuronal cell death and subsequently lead to neurodegeneration. Auricularia polytricha (AP) is an edible mushroom with several medicinal properties. Herein, the anti-neuroinflammatory effects of AP extracts against BPA-induced BV2 microglial inflammation were investigated. Hexane (APH) and ethanol (APE) extracts of AP inhibited BPA-induced neuroinflammation in BV2 cells by reducing the expression of pro-inflammatory cytokines. These anti-inflammatory effects were regulated by the NF-κB signaling pathway. In addition, APH and APE exhibited antioxidative effects by increasing a superoxide dismutase-1 (SOD-1), an antioxidant enzyme, and restoring an accumulation of reactive oxygen species (ROS) in BPA-induced BV2 cells. Further, ergosterol was isolated from APE and also showed anti-inflammatory and antioxidative activities in BPA-induced BV2 cells. Besides, the neuroprotective effects of ergosterol against the TNF-α-induced HT-22 hippocampal cell injury were investigated. Ergosterol attenuated the toxicity of TNF-α on HT-22 cells, by increasing the expression of SOD-1 and by facilitating the scavenging of ROS through antioxidant signaling. Based on the antibody array, the phospho-Akt was activated in the presence of ergosterol, and this finding was also supported by Western blotting analysis. Furthermore, ergosterol inhibited the transcriptional expressions of the glutamate ionotropic receptor N-methyl-D-aspartate type subunit 2B gene (Grin2b) through an early growth response-1 (EGR-1) signaling in TNF-α-treated HT-22 cells. These findings demonstrate novel therapeutic activities of AP extracts and ergosterol in anti-neuroinflammation and neuroprotection that might be of benefit for patients with neurodegenerative diseases.