文献类型：期刊文献

英文题名：FA-2-b-β modulates HMGB1/NF-κB/NLRP3 signaling to alleviate neuroinflammation in Alzheimer's disease

作者：Zhang, Yamin[1,2];Wang, Jianping[3];Yuan, Jin[1];Li, Siyu[1];Sun, Yanqing[4]

第一作者：张艺梦;Zhang, Yamin

通信作者：Sun, YQ[1]

机构：[1]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[2]Gansu Prov Hosp, Neurol Dept, Lanzhou, Gansu, Peoples R China;[3]Gansu Prov Hosp, Emergency Dept, Lanzhou, Gansu, Peoples R China;[4]Gansu Prov Hosp, Clin Teaching Dept, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp, Clin Teaching Dept, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2026

外文期刊名：JOURNAL OF ALZHEIMERS DISEASE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001686466200001)】；

基金：This study was supported by Gansu provincial joint research fund of science and technology planning project (24JRRA890).

语种：英文

外文关键词：Alzheimer's disease; FA-2-b-beta; HMGB1; NLRP3 inflammasome; pyroptosis

摘要：Background FA-2-b-beta, an extract derived from traditional Chinese medicine (TCM), has been suggested as a potential neuroprotective agent.Objective This study aimed to elucidate its role in modulating HMGB1-mediated inflammation and pyroptosis in Alzheimer's disease (AD), with a particular emphasis on the interaction between FA-2-b-beta and HMGB1.Methods AD cell and animal models were used to examine the effect of FA-2-b-beta on HMGB1/NF-kappa B/NLRP3 signaling pathway. Protein expression levels were detected by western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Immunofluorescence staining was performed to determine the cellular localization of key proteins. The role of HMGB1 in amyloid-beta (A beta)-induced neuroinflammation and pyroptosis was examined through siRNA-mediated HMGB1 knockdown. Behavioral tests were conducted in AD animal models to evaluate cognitive improvements following FA-2-b-beta treatment.Results In cellular models, FA-2-b-beta significantly suppressed A beta-induced overexpression HMGB1 and inhibited the activation of NF-kappa B, which consequently led to a reduction in the formation of the NLRP3 inflammasome. This suppression resulted in decreased of activation caspase-1 and lower levels of IL-1 beta and IL-18, thereby alleviating pyroptosis and neuroinflammation. The knockdown of HMGB1 further corroborated its role in mediating A beta-induced inflammatory responses. In AD animal models, treatment with FA-2-b-beta attenuated neuroinflammation, preserved neuronal integrity, and enhanced cognitive function.Conclusions FA-2-b-beta exhibits a capacity to modulate the HMGB1/NF-kappa B/NLRP3 signaling pathway, thereby mitigating neuroinflammation and pyroptosis, highlighting its potential as a therapeutic intervention for AD.