Diammonium Glycyrrhizinate Attenuates Aβ1-42-Induced Neuroinflammation and Regulates MAPK and NF-κB Pathways In Vitro and In Vivo

Background and purpose Beta-amyloid (A beta)-mediated inflammation contributes to the progression and chronicity of Alzheimer's disease (AD), although the exact mechanism remains unclear. This study aimed to investigate whether diammonium glycyrrhizinate (DG) could inhibit A beta-induced inflammation in vitro and in vivo and to explore the underlying mechanisms. Methods A beta 142 was injected to bilateral hippocampus of mice to make the AD models in vivo. The levels of mRNA and protein of inflammatory cytokines were measured by real-time PCR and Western blotting, respectively. The viability of SH-SY5Y and HT-22 cells was determined by MTT. NF-kappa B p65 translocation was analyzed by Western blotting and immunostaining. Phosphorylation of ERK, p38, and JNK was tested by Western blotting. Results DG suppressed A beta 142-induced activation of microglia and inflammation in vitro and in vivo. The media from A beta 142-activated microglia decreased the viability of SH-SY5Y and HT-22 cells, but it was rescued when pretreated with DG. DG could inhibit the activation of MAPK and NF-kappa B signaling pathways and attenuate the memory deficits in A beta 142-induced AD mice. Conclusions DG protects A beta 142-induced AD models in vitro and in vivo through reducing activation of microglia and inflammation, which may be involved in MAPK and NF-kappa B pathways.