摘要Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its precise mechanism in treating post-CHF cognitive dys-function remains unclear.This study systematically investigates XJQ's effects on post-CHF cognitive dysfunction and the underlying mechanisms.The components of XJQ were identi-fied through liquid chromatography-mass spectrometry.CHF was induced in rats via ligation of the left anterior descending coronary artery,followed by six weeks of XJQ treatment.Cardi-ac function was evaluated through echocardiography and hemodynamic parameters,while cognitive function was assessed using Morris water maze(MWM)and open field tests(OFT).XJQ treatment enhanced both cardiac and cognitive functions in CHF rats.Network pharmaco-logy identified 12 core active components of XJQ and indicated its effect on cognitive dysfunc-tion involved regulating synapses,inflammation,and phosphodiesterase 4(PDE4)-depend-ent cyclic adenosine monophosphate(cAMP)signaling.XJQ inhibited microglial and astrocyte activation,decreased proinflammatory cytokines,and mitigated neuronal damage.Notably,XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulat-ing cAMP,protein kinase A(PKA),cAMP-response element binding protein(CREB),brain-de-rived neurotrophic factor(BDNF),PSD95,and synapsin I levels.Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin,kaempferol,isorhamnetin,and darutoside to PDE4.In conclusion,XJQ alleviates neuroinflammation and enhances syn-aptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway.These findings provide valuable insight into the heart-brain axis.