Diammonium glycyrrhizinate attenuates Aβ(1-42) -induced neuroinflammation and regulates MAPK and NF-κB pathways in vitro and in vivo

Abstract

Background and purpose: Beta-amyloid (Aβ)-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 Aβ-induced inflammation in vitro and in vivo and to explore the underlying mechanisms.

Methods: Aβ(1-42) 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-κB p65 translocation was analyzed by Western blotting and immunostaining. Phosphorylation of ERK, p38, and JNK was tested by Western blotting.

Results: DG suppressed Aβ(1-42) -induced activation of microglia and inflammation in vitro and in vivo. The media from Aβ(1-42) -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-κB signaling pathways and attenuate the memory deficits in Aβ(1-42) -induced AD mice.

Conclusions: DG protects Aβ(1-42) -induced AD models in vitro and in vivo through reducing activation of microglia and inflammation, which may be involved in MAPK and NF-κB pathways.