Comparative cardioprotective effects of licorice-processed aconite(Zhifuzi)and Heishunpian in chronic heart failure:Integration of blood-entry component profiling,network pharmacology,and molecular dockingOA

Background:Aconiti radix lateralis praeparata(Fuzi)is widely used for cardiotonic therapy in traditional Chinese medicine,but is limited by toxicity.Licorice-processed aconite(Zhifuzi,ZFZ)is classical processing intended to reduce toxicity while preserving efficacy,yet its comparative effects with HSP and underlying mechanisms in chronic heart failure(CHF)remain unclear.Methods:A rat CHF model was established by abdominal aortic coarctation.After model validation by echocardiography(EF≤55%),animals received HSP or ZFZ at low,medium and high doses,Shenfu Qiangxin Pills(SFQX)as a positive control,or vehicle for 4 weeks.Cardiac function,plasma biomarkers(BNP,AngII,CK),inflammatory cytokines in cardiac tissue(TNF-α,IL-6,IL-10),and histopathology(HE,Masson staining)were assessed.Blood-entry components of ZFZ were profiled by UPLC-Q Exactive-Orbitrap-MS,followed by target prediction,protein–protein interaction analysis,GO/KEGG enrichment and molecular docking.Results:Both ZFZ and HSP improved cardiac function,reduced plasma BNP,Ang II,and CK levels,alleviated inflammatory responses,and attenuated myocardial fibrosis in CHF rats.ZFZ showed relatively better effects than HSP in selected parameters,particularly in the high-dose group.Thirty-one blood-entry metabolites were detected,including 16 prototype compounds.Network pharmacology suggested that alkaloids,flavonoids and triterpenoids target multiple proteins enriched in PI3K–Akt,cAMP and calcium signaling pathways.Docking indicated that talatisamine,oleanolic acid and hetisine exhibited stable binding to MAPK1,PIK3CA and PRKACA,respectively.Conclusion:ZFZ and HSP both exerted cardioprotective effects in CHF rats,while ZFZ showed relatively better effects in selected parameters under the present experimental conditions.The integrated analysis of blood-entry component profiling,network pharmacology,and molecular docking provided preliminary mechanistic clues suggesting that the cardioprotective effects of ZFZ may be associated with multiple components,targets,and pathways.These findings provide comparative pharmacodynamic evidence and a basis for further mechanistic investigation of processed Fuzi in chronic heart failure.