Effects Of Xin-Ji-Er-Kang On High Salt-induced Heart Failure And Kidney Injury In Mice

Background:At present,current clinical studies have found that excessive salt intake greatly increases the risk of cardiovascular disease.Xin-Ji-Er-Kang（XJEK）is a traditional Chinese herbal medicine.It is composed of ginseng,astragalus,Ophiopogon japonicus,Polygonatum odoratum and other precious medicinal materials.It has been used for many years and has been demonstrated in model mice of myocardial infarction.Effective protection of heart function and kidney function.Objective:We investigated the effects of XJEK on cardiovascular-and renal-function in a high salt（HS）-induced heart failure mouse model and associated mechanisms.Methods:To evaluate the effects of XJEK in a hypertensive heart failure model,mice were fed with 8%high salt diet.XJEK was administered by oral gavage for8-weeks.Cardiovascular function parameters,renal function associated biomarkers and XJEK’s impact on renin-angiotensin–aldosterone system（RAAS）activation were assessed.To determine the underlying mechanism,the calpain1/junctophilin-2（JP2）/sarcoplasmic reticulum Ca²⁺ATPase（SERCA2a）pathway was further studied in AC16 cell after Angiotensin II-challenge or after Calpastatinsmall interfering RNA（si RNA）transfection.Results:Mice on HS-diet exhibited hypertensive heart failure along with progressive kidney injury.Similar to fosinopril,XJEK ameliorated hypertension,cardiovascular-and renal-dysfunction in mice on HS-diet group.XJEK inhibited HS-induced activation of RAAS and reversed the abnormal expression pattern of Calpain1and JP2 protein in heart tissue.XJEK significantly improved cell viability in Angiotensin II-challenged AC16 cells.Moreover,XJEK’s impact on Calpain1/JP2 pathway was partly diminished in AC16 cells transfected with Calpastatin si RNA.Conclusion:We found that XJEK exerted cardiovascular-and renal protection in HS-diet induced heart failure model.And XJEK inhibited HS-diet induced RAAS activation by inhibiting the activity and expression of Calpain1 and protected the junctional membrane complex（JMC）in cardiomyocytes.