Efficacy of Zhenwu Decoction Plus Guizhi Fuling Pills in the Treatment of Chronic Heart Failure with the Syndrome of Fluid Retention due to Yang Deficiency and Its Network Pharmacological Study
Objective To observe the clinical efficacy of Zhenwu Decoction plus Guizhi Fuling Pills in the treatment of patients with chronic heart failure(CHF)of fluid retention due to yang deficiency type,and to explore its therapeutic mechanism by network pharmacology.Methods A total of 64 cases of CHF patients with fluid retention due to yang deficiency type were randomly divided into treatment group and control group,with 32 cases in each group.The control group was given the basic western medicine treatment,and the treatment group was treated with Zhenwu Decoction plus Guizhi Fuling Pills on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,echocardiographic parameters,distance of 6-minute walking test(6MWT),Minnesota Living with Heart Failure Questionnaire(MLHFQ)score,and serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP)and omentin-1 in the two groups were observed before and after treatment.After treatment,the efficacy for TCM syndrome was compared between the two groups.The active components,component targets and CHF disease targets of Zhenwu Decoction plus Guizhi Fuling Pills were obtained from the relevant databases by using the network pharmacological methods.After the intersection targets were obtained,the intersection target protein-protein interaction network was constructed and the enrichment analysis was carried out to predict the therapeutic mechanism of Zhenwu Decoction plus Guizhi Fuling Pills for CHF.Results(1)After 4 weeks of treatment,the total effective rate of the treatment group was 90.62%(29/32),and that of the control group was 71.87%(23/32).The intergroup comparison(tested by chi-square test)showed that the efficacy for TCM syndrome in the treatment group was significantly superior to that in the control group(P<0.05).(2)After treatment,the scores of TCM syndromes such as shortness of breath/wheezing,palpitation,aversion to cold and cold limbs,facial edema and edema of limbs,fatigue,darkish-purple lip and nails,gloomy complexion,oliguria and cough as well as the total scores in the two groups were decreased when compared with those before treatment(P<0.01),and the decrease of the scores of shortness of breath/wheezing,aversion to cold and cold limbs,facial edema and edema of limbs,fatigue,darkish-purple lip and nails,gloomy complexion and oliguria as well as the total scores in the treatment group was superior to that in the control group(P<0.05 or P<0.01).(3)After treatment,the left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)in the two groups were decreased when compared with those before treatment(P<0.01),and the left ventricular ejection fraction(LVEF)was increased when compared with that before treatment(P<0.01).Moreover,the decrease in LVEDD and LVESD and the increase in LVEF in the treatment group were superior to those in the control group(P<0.01).(4)After treatment,the 6MWT distance in the two groups was increased(P<0.01)and the MLHFQ score was decreased(P<0.01)when compared with that before treatment,and the increase of 6MWT distance and the decrease of MLHFQ score in the treatment group were significantly superior to those in the control group(P<0.01).(5)After treatment,the serum NT-proBNP level in the two groups was decreased(P<0.01)and the serum omentin-1 level was increased when compared with that before treatment(P<0.01).The intergroup comparison showed that the decrease of NT-proBNP level and the increase of Omentin-1 level in the treatment group were superior to those in the control group(P<0.01).(6)A total of 106 active components and 818 targets of Zhenwu Decoction plus Guizhi Fuling Pills as well as 10 660 disease genes of CHF were obtained.A total of 21 network core targets such as NOS3,TP53,MMP9,VEGFA,IL6,TNF,and CASP3 were screened.The enriched analysis yielded the therapeutic pathways of renin secretion,cyclic guanosine monophosphate-protein kinase(cGMP-PKG)signaling pathway,hypoxia-inducible factor 1(HIF-1)pathway,calcium signaling pathway,Th17 cell differentiation,advanced glycation end products and their receptors(AGE-RAGE)signaling pathway,insulin resistance and so on.Conclusion Zhenwu Decoction plus Guizhi Fuling Pills exert certain effect on CHF.It is effective on inhibiting the inflammatory response,decreasing cardiac load and improving ventricular remodeling through the multi-component,multi-target and multi-pathway mechanism of Chinese medicine,so as to effectively relieve the clinical symptoms of patients and improve the quality of life and prognosis of the CHF patients.
fluid retention due to yang deficiency syndromechronic heart failureZhenwu DecoctionGuizhi Fuling Pillsomentin-1network pharmacologyquality of lifeinflammatory responsecardiac loadventricular remodeling