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Astragalus monomers treatment ameliorates angiotensin II-induced impairment of human umbilical vein endothelial cellsObjectives: To investigate the efficacy of four astragalus extacts,calycosin-7-O-?-D-glucoside,calycosin,formononetin and Astragaloside IV on the dysfunction of human umbilical vein endothelial cell(HUVEC)induced by angiotensin ?(Ang ?).Methods:Cultured HUVEC were randomly divided into several groups: control,Ang?(10 ?mol·L-1)alone,Ang?(10 ?mol·L-1)plus calycosin-7-O-?-D-glucoside,calycosin,formononetin,Astragaloside IV or Irbesartan10 ?mol·L-1respectively.Seven groups of cells were cultured for 24 hours.The apoptosis of the cells was measured by flow cytometry with Annexin V-FITC/PI double staining.Genes transcriptionof endothelial nitric oxide synthase and endothelin-1 were detected by real-time polymerase chain reaction techniques.Results: The apoptosis ratio of Calycosin-7-O-?-D-glucoside,calycosinand Astragaloside IV was(11.63 ± 0.38)%,(8.25 ± 0.14)%and(9.77 ± 0.39)% respectively,decreased significantly compared with Ang? group(P=0.0350,P=0.0114,P=0.0303 respectively).There was no significant difference in the apoptosis ratio between the formononetin group(12.50 ± 0.84)% and Ang II group(15.54 ± 0.58)%(P=0.0569).The expression of e NOS m RNA in the calycosin-7-O-?-D-glucoside group and calycosin group was significantly higher than that of Ang II group at the 24 th hour(P= 0.0077,P=0.0003 respectively),but there was no significant difference between astragaloside IV group and Ang II group(P=0.0942).Calycosin-7-O-?-D-glucoside could reduce the increase of ET-1 m RNA level induced by Ang? at 6th hour,12 th hour and 24 th hour(P = 0.0034,P =0.0022,P = 0.0020 respectively);Compared with Ang?group,ET-1 m RNA level in calycosin group decreased significantly at 6th hour,12 th hour and 24 th hour(P<0.0001,P<0.0001,P=0.0010 respectively);The expression levels of ET-1 m RNA in the astragaloside IV group was lower than that of Ang II group at 12 th and 24 th hour(P=0.0106,P=0.212,respectively).Conclusion:The monomers of Radix Astragali,calycosin-7-O-?-D-glucoside,calycosin and astragaloside IV can reduce the apoptosis of HUVEC and the expression of ET-1 m RNA induced by Ang II,calycosin-7-O-?-D-glucoside and calycosin can increase the expression of e NOS m RNA in HUVEC.However,formononetin can not reduce the dysfunction of HUVEC induced by Ang?.Part ? A randomized controlled clinical study of the effect of astragalus extract tablets on cardiac and vascular function in hypertensive patients with metabolic syndromeObjective:To observe the effect of astragalus membranaceus cultivated in Longxi,Gansu province on subclinical vascular damage and cardiac diastolic function in patients with hypertension and metabolic syndrome(Met S),and investigate the protective effect of astragalus membranaceus on cardiovascular damage induced by hypertension and Met S.Methods: Hypertensive patients with Met S were randomly divided into control group,astragalus low dose group and Astragalus high dose group.The control group was given routine medical treatment,while astragalus groups were given astragalus extract tablets for 10g/ days or 5g/ days on the basis of routine medical treatment respectively.Mets components,arterial stiffness and diastolic function were determined at baseline,sixth months and twelfth months respectively.Carotid-femoral pulse wave velocity(cf PWV),cardio-ankle vascular index(CAVI),carotid intima media thickness(c IMT)and ankle-brachial index(ABI)were measured as indicators of subclinical vascular damage.Left atrium maximum volume index(LAVI),mitral valvular early diastolic inflow velocity(E),early diastolic mitral annular velocity(e')and tricuspid regurgitationinflow velocity were measured to assess left ventricular diastolic function.Waist circumference,blood pressure,serum glucose and lipid,liver function,renal function,and microalbuminuria(MAU)were determined.Results: 191 patients with hypertension and Met S were followed up.After the treatment of astragali radix for one year,there was no significant difference between the treatment and the control group in each Met S components.Compared with control group,the cf PWV reduced in both the high and the low dose groups of astragalus extract tablets after one year(F=3.308,P=0.039),the effect of low dose astragali radix on reducing cf PWV is comparable with that of the high dose group(P=0.725);Consitstantly,compared with baseline,there were no significant changes neither in the high dose group nor the low dose group(F=1.640,P=0.195).Howerver,compared with control group,both right and left CAVI reduced in the high dose group and the low dose group of Astragali radix after one year treatment(F=3.481,P=0.033;F=3.575,P=0.030),the effect of the small dose astragali radix on reducing right or left CAVI is not significant compared to that of the high dose group(P=0.459,P=0.740 respectively);Notably,compared with baseline,there were no significant changes neither in the high nor low dose group(F=0.981,P=0.376;F=3.575,P=0.030);ABI and c IMT did not change compared with the control group or baseline after the treatment of six or twelve months(P>0.05).Compared with baseline,lateral e? increased at half and one year in both the high and low dose groups(F=4.378,P=0.013),while the other diastolic function parameters did not change(P>0.05).In addition,the MAU reduced in the high and low dose group of Astragalus after half year and one year compared with control group and baseline(F=13.572,P<0.001;F =30.621,P<0.001).However,other parameters of liver and kidney function did not change(P>0.05).Conclusions: On the basis of a routine medical treatment,astragalus extract tablets did not effectively affect Mets components.However,the long term low dosage could significantly reduce arterial stiffness in patients with hypertension and Met S,the effect of the low dose was comparable to that of the higher one.Part ? Effects of angiotensin converting enzyme inhibitors on arterial stiffness: a systematic review and meta-analysis of randomized controlled trialsObjective: To determine the effects of Angiotensin converting enzyme inhibitors(ACEIs)on arterial stiffness,we conducted a systematic review and meta-analysis of randomized controlled trials(RCTs)to determine the effects of ACEIs on arterial stiffness.Methods: Systematic retrieving of the relevant articles investigated the effect of ACEIs on arterial stiffness from Pub Med,Embase,and the Cochrane library from inception to September 2018.The investigated outcomes including brachial-ankle pulse wave velocity(ba-PWV)and carotid-femoral PWV(cf-PWV)by using weighted mean differences(WMDs)and 95% confidence intervals(CIs)with random-effects model.Results: A total of 17 RCTs included 1,458 individuals were included in final analysis.The summary results indicated no significant differences between ACEIs and control for ba-PWV(WMD:-0.35;95% CI:-2.06 to 1.36;P = 0.688)and cf-PWV(WMD:-0.44;95% CI:-0.96 to 0.09;P = 0.104).Also no significant differences between ACEI and control for ba-PWV(WMD: 0.31;95%CI:-0.48 to 1.10;P=0.443)and cf-PWV(WMD:-0.13;95%CI:-0.54 to 0.27;P=0.528)were observed in hypertensive patients.while the therapeutic effects of ACEI versus placebo showed statistically significant difference,and ACEIs was associated with lower ba-PWV(WMD:-2.40;95%CI:-2.54 to-2.26;P<0.001)and lower cf-PWV(WMD:-2.05;95%CI:-2.15 to-1.94;P<0.001).Moreover,subgroup analysis indicated the level of ba-PWV were associated with statistically significant if the study conducted in Western countries,mean age < 60.0 years,percentage male ? 60.0%,compared with ARB,baseline PWV<10.0,and study with high quality.Furthermore,the significant levels of cf-PWV in patients who received ACEIs were observed when percentage male was ?60.0%,and high quality studies.All the included studies reported systolic blood pressure(SBP)and diastolic blood pressure(DBP)at baseline and after interventions.The summary WMD indicated that patients who received ACEI showed no significant difference in SBP compared with the control group(WMD:-0.70;95%CI:-2.72 to 1.33;P = 0.500;Furthermore,no significant difference was observed between ACEI and control groups regarding the change of DBP (WMD: 0.26;95%CI:-1.50 to 2.02;P = 0.772).Conclusions: The overall analysis of this study suggested no significant differences between ACEIs and other antihypertensive drugs for ba-PWV and cf-PWV levels,whereas ACEIs versus placebo shows lower levels of ba-PWV and cf-PWV. |
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