Inhibition Of Heart Failure And The Involved Mechanisms By Xian Gui Capsule And LCZ696

Heart failure(HF)is a clinical syndrome caused by changes in the structure and function of the heart.Its morbidity and mortality are high,resulting in frequent hospitalizations that will greatly reduce the quality of life of patients.LCZ696 is the angiotensin receptor-enkephalinase inhibitor,which can significantly reduce the morbidity and mortality of patients with heart failure.Xian Gui capsule(XG)is a traditional Chinese medicine.Studies have found that XG has protective effects on the cardiovascular system.In this topic,we used the heart failure mouse model to explore the therapeutic effects of XG,LCZ696 and the co-treatment on heart failure,as well as the involved mechanisms.In the experiment,male C57BL/6J mice aged 6-8 weeks were randomly divided into5 groups with 8 mice in each group.They are the control group,doxorubicin(DOX)group,LCZ696 group,Xian Gui capsule group and co-treatment group.The control group was fed with normal food and intraperitoneal injection of PBS every week;the other groups were injection of 5 mg/kg DOX every week for 4 weeks;the LCZ696 group was fed with normal food and given daily oral gavage LCZ696;XG group,fed food containing XG every day;co-treatment group was oral gavage LCZ696 and fed food containing XG every day.At the end of experiment,the mice serum and heart tissue were extracted to research the effects and mechanisms of heart failure.This study demonstrates that LCZ696 and XG treatment can significantly improve the heart function of mice,regulate blood pressure,reduce the levels of biomarkers related to cardiac injury,and inhibit the myocardial fibrosis,cardiomyocyte oxidative stress,and oxidative stress induced by DOX in mice.After co-treatment,the effect of improving heart failure was further enhanced.From a mechanism point of view,LCZ696,XG and cotreatment inhibit α-smooth muscle actin(α-SMA),collagen type I A1(COL1A1),transforming growth factor β1(TGF-β1)expression to alleviate myocardial fibrosis.At the same time,XG,LCZ696 and their co-treament also increased catalase(CAT),forkhead box O3a(FOXO3a)and superoxide dismutase 1/2(SOD1/2)levels,thereby reduce DOXinduced oxidative stress.In addition,XG,LCZ696 and XG plus LCZ696 can significantly attenuates interleukin-1β or 6 or 10(IL-1 β/6/10)and nuclear factor κB(NF-κB),toll-like4(TLR4),tumor necrosis factor α(TNF-α)and regulate apoptosis-related factor B-cell lymphoma-2(BCL-2)and BCL-2 related X protein(BAX)expression.Our study also found that LCZ696 treatment can cause hypotension in mice with heart failure,and XG can effectively antagonize this side effect.In summary,results showed the XG,LCZ696 and XG plus LCZ696 can significantly improve the heart function of mice,relieve myocardial damage and inhibit myocardial fibrosis,has multiple cardioprotective functions.In mechanism,co-treatment protects heart failure by reducing inflammation,increasing the expression of antioxidant enzymes and inhibiting cardiomyocyte apoptosis.More importantly,XG can improve the side effects of low blood pressure caused by LCZ696,indicating that LCZ696 plus XG may have excellent clinical application potential.