Licochalcone A Ameliorates Cognitive Dysfunction in an Alzheimer's Disease Model by Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.

This article investigates the therapeutic potential of licochalcone A (Lico A), a flavonoid derived from Glycyrrhiza species, in ameliorating cognitive impairment in Alzheimer's disease (AD) by targeting endoplasmic reticulum (ER) stress-induced neuronal apoptosis. Using triple transgenic AD mouse models and primary hippocampal neurons, the study demonstrates that Lico A treatment reduces amyloid beta (Aβ) plaque deposition, inhibits ER stress markers—including Bip (GRP78), phosphorylated eIF2α, ATF4, and CHOP—and decreases neuronal apoptosis, thereby improving cognitive function. Mechanistically, Lico A's neuroprotective effects involve activation of the Nrf2 and PI3K/AKT signaling pathways and suppression of the PERK/eIF2α/ATF4/CHOP pathway. Pharmacokinetic analysis indicates good bioavailability and low toxicity of Lico A in AD mice, supporting its potential as a safe therapeutic agent for AD.