摘要Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardi-ovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol(ISO)con-tinuous stimulation-induced chronic heart failure(CHF)in mice,providing direct experiment-al evidence for further clinical applications.In vivo,continuous ISO infusion was administered to mice,and ventricular myocytes were utilized to explore LGZG's potential mechanism of ac-tion on the β1-adrenergic receptor(β1-AR)/Gs/G protein-coupled receptor kinases(GRKs)/β-arrestin signaling deflection system in the heart.The findings reveal that LGZG significantly reduced the messenger ribonucleic acid(mRNA)expression of hypertrophy-related biomark-ers[atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)]and improved car-diac remodeling and left ventricular diastolic function in mice with ISO-induced CHF.Further-more,LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate(cAMP)/pro-tein kinase A(PKA)signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein(CREB)and the expression of the coactivator CBP/P300.Notably,LGZG downregulated the expression of β-arrestin1 and GRK 2/3/5 while upregulating the expression of β1-AR and β-arrestin2.These results suggest that LGZG inhib-its Gs/cAMP/PKA signaling and β-arrestin/GRK-mediated desensitization and internalization of β1-AR,potentially exerting cardioprotective effects through the synergistic regulation of the β1-AR/Gs/GRKs/β-arrestin signaling deflection system via multiple pathways.