Hyodeoxycholic acid rescues lipopolysaccharide-induced neuroinflammation via regulating TGR5/AKT/NF-κB pathway

Abstract

Hyodeoxycholic acid (HDCA) is a natural secondary bile acid with enormous pharmacological effects. It can act as a takeda G-coupled protein receptor 5 (TGR5) agonist, activation of TGR5 is found to alleviate neuroinflammation by suppressing serine/threonine kinase (AKT)/ nuclear factor-κB (NF-κB) signaling pathway. In this study, the anti-microglial inflammatory effect of HDCA was evaluated in lipopolysaccharide (LPS)-induced BV2 microglial cells and mice (n=12/group). One-way ANOVA followed by Tukey’s post hoc analysis was conducted. p <.05 is statistically significant. HDCA was shown to inhibit the over-activation of microglia both in vitro and in vivo , evidenced by down-regulated mRNA expression of inflammatory cytokines such as interleukin 1β, decreased protein expression of inducible nitric oxide synthase and cyclooxygenase 2. Moreover, in LPS-induced microglial cells, HDCA was found to counteract the suppression of TGR5 and the increased phosphorylation of AKT, NF-κB and NF-κB inhibitor factor, as well as the nuclear translocation of NF-κB, however, the effect of HDCA onTGR5, AKT and NF-κB was abolished by the TGR5 inhibitor - triamterene. HDCA suppresses LPS-induced neuroinflammation through regulating TGR5/AKT/NF-κB signaling pathway. The novel findings suggest the therapeutic potential of HDCA in central nervous system disorders with prominent neuroinflammation.