Effect And Mechanism Of Tianhuang Formula And Kaempferol On Heart And Kidney Injury Induced By Hypertensive

Objective:The purpose of this study is to evaluate the overall efficacy of Tian huang formula on DOCA/salt induced hypertension and cadio-renal injury,and to explore its possible molecular mechanism,so as to provide a theoretical basis for Tianhuang formula in the prevention and treatment of hypertension.Methods:1.Study on the effect of Tianhuang formula on prevention and treatment of hypertension based on network pharmacologyPredict the target,effective material basis and action pathway of Tianhuang formula in the treatment of hypertension based on network pharmacology.The active components and targets of Tianhuang formula was screened from TCMSP,UniProt and Swiss Target Prediction databases,and the hypertension target genes were obtained from Genecards,OMIM and DrugBank database.The protein interaction network between disease targets and PPI network of Tianhuang formula active component targets were constructed based on Cytoscape software,and then the core targets were obtained.Finally,the functional enrichment analysis of the core target and the molecular docking of Tianhuang formula active components and targets were carried out.2.Effect of Tianhuang formula on hypertensive heart and kidney injuryThirty five male Sprague Dawley(SD)rats were randomly divided into five groups: control group(control),DOCA/salt hypertension group(model),DOCA/salt + Tianhuang formula low-dose group(100 mg/kg/d,THF-L),DOCA/salt + Tianhuang formula high-dose group(200 mg/kg/d,THF-H)and captopril group(30 mg/kg/d).The right kidney was removed from all rats.In addition to the sham operation in the control group,the rats in other groups were implanted subcutaneously with deoxycorticosterone acetate(DOCA,150 mg/rat)and given 1% Na Cl(pure water in Ctrl group)to establish the hypertensive rat model for 4weeks.Blood pressure was monitored by tail cuff method during the experiment.The expression of cardiac and renal fibrosis,inflammatory factors and oxidative stress factors and the changes of serum creatinine(Scr)and blood urea nitrogen(BUN)were detected,and the pathological damage of heart and kidney were observed.3.Study on the efficacy and mechanism of kaempferol on hypertensive renal injuryThree groups were set up: control group(control),DOCA/salt hypertension group(model)and kaempferol group(100 mg/kg/d).The molding process is consistent with the above.The pathological injury of kidney was observed,the expression of renal fibrosis,inflammatory factors and oxidative stress factors and the changes of Scr and BUN in serum were detected.Result:1.Study on the effect of Tianhuang formula on prevention and treatment of hypertension based on network pharmacologyThis study screened out the potential active components of Tianhuang formula for the treatment of hypertension through network pharmacology,such as berberine,quercetin,coptisine,ginsenoside f2,ginsenoside Rh2,beta-sitosterol,etc;Potential core targets TNF,AKT1,VCAM1,EGFR,PI3 K,TGF-β1,IL-17,etc;The main action pathways are Pathways in cancer signaling pathway,PIP3-Akt signaling pathway and TGF-β1 signal pathway,etc.Molecular docking showed the effect of kaempferol on TGF-β1 and related targets have better binding ability.2.Effect of Tianhuang formula on hypertensive heart and kidney injuryBoth high and low doses of Tianhuang formula can significantly reduce blood pressure induced by DOCA/salt,inhibit the increase of BUN,improve renal function,reduce the damage of cardiac and renal fibrosis,and reduce the expression of proinflammatory factors,chemokines and oxidative stress factors in cardiac and renal tissues.At the same time,Tianhuang formula down regulated TGF-β1 and β-arrestin1 expression of protein and mRNA.3.Study on the efficacy and mechanism of kaempferol on hypertensive renal injuryKaempferol can significantly reduce blood pressure,inhibit the levels of Scr and BUN,improve renal function,reduce fibrosis injury and intrarenal inflammation,inhibit oxidative stress factor NOX3 and has no effect NOX1 and NOX2.Meanwhile,kaempferol down regulated expression of TGF-β1 and β-arrestin1 protein and mRNA.Conclusion:Tianhuang formula has the advantages of multi-component and multi-target synergy in the prevention and treatment of hypertension.It can inhibit the increase of blood pressure induced by DOCA/salt in rats and protect heart and kidney injury.Kaempferol has a protective effect on DOCA/salt hypertension and renal injury.