生物信息学与实验验证结合解析加味芎归汤改善高胆固醇血症相关性认知障碍的机制OA

Aim To investigate the therapeutic effects of Jiawei Xionggui decoction(JWXG)on hypercholesterolemia-related cognitive impairment(HRCI)using an integrated approach combining bioin-formatics and animal experiments and the underlying mechanisms.Methods The blood-absorbed compo-nents of JWXG were identified by high-resolution mass spectrometry.Network pharmacology,molecular dock-ing,and molecular dynamics simulations were em-ployed to predict core targets of these components against HRCI.Transcriptomic data from brain tissues of high-cholesterol diet(HCD)model mice in public databases were analyzed to identify differentially ex-pressed genes.An HRCI mouse model was established using a high-cholesterol diet and treated with JWXG aqueous extract via gavage.Serum cholesterol levels were measured using assay kits,cognitive function was assessed with the Morris water maze,neural pathologi-cal damage was evaluated by HE staining,key protein expression was detected via Western blot,and neuro-nal apoptosis was examined by TUNEL staining.Re-sults The main blood-absorbed components of JWXG included baicalein,baicalin,catalpol,chrysin,wogo-nin,and ferulic acid.KEGG and GO enrichment analyses of core targets revealed a focus on the apopto-sis pathway.Molecular docking and dynamics simula-tions demonstrated strong binding affinities of baicalin and catalpol to Bax and Bcl-2.Transcriptomic data in-dicated high expression of the Bax gene in the brain tis-sues of HCD mice.Animal experiments showed that JWXG significantly reduced serum cholesterol levels,improved learning and memory abilities,and allevi-ated hippocampal neuropathological damage in HRCI mice.JWXG also markedly increased the Bcl-2/Bax protein ratio and decreased the number of TUNEL-positive cells in the cortex of HRCI mice.Conclu-sion JWXG exerts neuroprotective effects and ame-liorates HRCI by antagonizing neuronal apoptosis.