Glycyrrhizic Acid From Glycyrrhiza uralensis Fish: A Novel Therapeutic Candidate for Alzheimer's Disease Targeting the JNK Signaling Pathway.

Alzheimer's disease (AD) has emerged as a prevalent public health concern. This study aims to investigate the mechanism of Glycyrrhiza uralensis Fish. in AD through the utilization of network pharmacology, molecular docking, and in vitro validation techniques. Based on gene expression, a gene network was constructed to identify the core target genes related to Aβ and Tau, and the effective compounds of G. uralensis Fisch. were screened by contribution index (CI), which reflects the relative importance of each gene for Aβ/Tau. Molecular docking analysis revealed that glycyrrhizic acid (GA) strongly binds to these core targets. Next, an in vitro model of AD was established by inducing microglia with Aβ1-42. This model was used to assess the effects of GA on microglial apoptosis, migration, and inflammation. RT-qPCR (real time quantitative polymerase chain reaction) results indicated that GA lowered the expression of Tbk1 (TANK-binding kinase 1) and Soat1 (sterol O-acyltransferase 1) while simultaneously increasing the expression of Slc2a3 (solute carrier family 2 member 3). Additionally, Western Blot results suggested that GA inhibited the JNK signaling pathway. This demonstrates its anti-apoptotic and anti-inflammatory properties. Therefore, GA, through its modulation of key signaling pathways and gene expression, is expected to be a potential therapeutic candidate for AD. This study reveals that GA, a key compound in G. uralensis Fish, alleviates AD pathology by targeting Aβ/Tau-related genes (Tbk1, Soat1, and Slc2a3) and inhibiting the JNK pathway.