Liquiritigenin Decreases Aβ Levels and Ameliorates Cognitive Decline by Regulating Microglia M1/M2 Transformation in AD Mice

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is currently incurable. Amyloid beta protein (A beta) deposition is the main pathogenesis of AD, and many studies have shown that A beta accumulation is toxic to neurons, leading to the inflammatory reaction, neuronal apoptosis, and neurofibrillary tangles. Thus, reducing A beta levels might be a potential therapeutic strategy for AD. Liquiritigenin (LG), a dihydroflavone monomer compound extracted from natural plant licorice, has a variety of biological activities such as antioxidant, anti-tumor, anti-inflammatory and anti-virus. However, the exact function of LG in the pathogenesis of AD is elusive. Here, we reported that LG could significantly attenuate neuronal apoptosis in A beta-induced N2A cells and APP/PS1 transgenic mice. Our in vivo and in vitro studies revealed that LG could alleviate the inflammation response, reflected by the reduction of NLRP3 and cleaved caspase-1. Meanwhile, we also found that LG was able to shift M1 type microglia towards M2 type microglia in A beta-induced BV2 cells and AD mice. Furthermore, LG could reduce the A beta levels by decreasing APP processing and accelerating A beta clearance in AD mice. More importantly, daily treatment of LG (30 mg/kg day) for 90 days dramatically ameliorated the spatial learning and memory of AD mice. Taken together, these results suggest that LG can reduce the A beta levels by regulating the M1/M2 transformation of microglia, thereby reversing memory decline during AD development, suggesting that LG may be a potential therapeutic agent for treating AD.

Automated summary

Our study demonstrated that liquiritigenin can alleviate Alzheimer's disease symptoms through multiple mechanisms, including reducing neuronal apoptosis, alleviating inflammation response, and promoting microglial type transformation. Furthermore, liquiritigenin may potentially treat AD by decreasing Aβ levels and improving spatial learning and memory.