[Protective effects of Astragalus membranaceus on free fatty acid-induced vascular endothelial cell dysfunction].

OBJECTIVE: To investigate whether Astragalus membranaceus (AM) can protect endothelium-dependent vasodilatation (EDV) function of aorta from the damage induced by high level of free fatty acid (FFA). METHODS: Ten male SD rats, 8 weeks old and 250-300 g in weight, were sacrificed and thoracic aorta were harvested. Aorta rings incubated in organ baths were divided into three groups, Control group, FFA group and FFA+ AM group. The control group was incubated in 20 mL Krebs-Henseleit solution; the FFA group was incubated in 20 mL KH solution mixed with FFA(800 micromol/L) the FFA + AM group was incubated in 20 mL KH solution mixed with FFA (800 micromol/L) and AM (4 g/L). The relaxation levels of aorta rings response to acetylcholine and sodium nitroprusside were measured, the expression of NF-kappaB and the level of NOx in the organ bath were analyzed by immunohistochemistry. RESULTS: Severe endothelial dysfunction were induced in FFA group (maximal vasorelaxation in response to Ach: 61.1% +/- l6.9% vs. 93.1% +/- 2.7% in control, P < 0.05), while EDV in FFA+AM group was significantly improved by the incubation with AM (P < 0.05). Compared with the control group (104.1 +/- 14.2) micromol/g, NOx levels of FFA group was (83.1 +/- 8.4) micromol/g (P < 0.05), and the treatment of AM increased the levels of NOx (98.8 +/- 10.7) micromol/g (P < 0.05). The control vascular ring had a little NF-kappaB expression in endothelial nucleus, FFA increased the activation of NF-kappaB, while the treatment of AM lower the elevated NF-kappaB level. CONCLUSION: FFA can directly injure EDV, while AM may ameliorate it, with the possible mechanism related to the signal pathway of NF-kappaB and NO.

[Astragalus membranaceus improves endothelial-dependent vasodilator function in obese rats].

OBJECTIVE: To investigate the effect of Astragalus membranaceus (AM) on endothelial-dependent (EDV) and non- dependent (EIV) vascular relaxation in ex vivo thoracic aortic rings of obese rats. METHODS: Fifteen SD rats were randomized into 3 equal groups, namely the control group fed with normal chow, obese group with high-fat chow, and AM intervention group fed with high-fat chow and daily AM gavage. The rats were sacrificed after 6 weeks of feeding, and the aortic rings were dissected and cut into 3-mm rings. The response to acethylcholine (Ach) and sodium nitroprusside (SNP) were examined in organ bath. In ex vivo study, the aortic rings obtained from the control group and obese group were incubated with AM or vehicle for 3 h in organ bath before testing the EDV and EIV. The body weight and weight of the visceral fat in each group were recorded. RESULTS: The weight of visceral fat was greater in the obese group than in the control group, and a 6-week AM treatment significantly reduced the fat tissue due to high-fat diet. The maximum EDV value was (87.0 - or + 3.5)% in the control group, (54.8 - or + 7.8)% in the obese group, and (69.8 - or + 5.7)% in AM intervention group; the EIV values were comparable between the 3 groups. After incubation with AM, the maximum EDV values of aortic rings obtained from the obese group were significantly increased from (55.6 - or + 8.3)% to (85.1 - or + 4.5)%. CONCLUSION: AM can improve endothelial dysfunction in obese rats, and the mechanism involves improved insulin resistance and increased endothelium-derived NO productor function.

[Radix Astragali improves impaired endothelial dependent vasodilation in obese rat].

OBJECTIVE: To investigate the effects of Radix Astragali, a traditional Chinese medicine, on endothelium-dependent and non-dependent vasodilation in food-induced obese SD rats. METHODS: Fifteen male Sprague-Dawley rats were divided into 3 groups. The control group (n=5) was fed with normal chow; The obese group (n=5) was fed with high fat chow; The Astragali group (n=5) was fed with high fat chow and Astragali in drinking water. At the end of six weeks, all rats were killed and heart blood samples were taken to assess serum triglyceride, total cholesterol, and free fat acid. The thoracic aortas rings were harvested and equilibrated in Krebs-Henseleit solution. To measure the endothelium-dependent relaxation, the aortas rings were constricted in response to norepinephrine. After a stable contraction plateau was reached, cumulative dose-response for relaxation to Acetylcholine (10(-8)-10(-4) mol/L) were obtained in each rings. Identical experiments were conducted with 10(-8)-10(-4) mol/L sodium nitroprusside as the endothelium independent vasorelaxting agent. Responses to vasodlilators were expressed as percentage relaxation in all preconstricted state. RESULTS: The ratio of celiac fat and body weight in the obese rats was higher than in the controls. The levels of serum triglyceride, total cholesterol, and free fat acid were elevated in the Obese Group compared with the Control Group. The Astragali Group had lower triglyceride and free fat acid levels than the Obese Group. Compared with the rats with high-fat diet, the rats fed with Astragali lost about 32% of celiac fat. Acetylcholine (10(-8)-10(-4) mol/L) caused a concentration-dependent relaxation in all preconstricted aortic rings. Compared to the control group, maximal endothelium dependent relaxation in the obese group was impaired (P<0.05). In the Astragali group, the relaxation to acetylcholine was intermediate between control and obese group (P<0.05). Sodium nitroprusside (10(-8)-10(-4) mol/L) induced potent relaxation (endothelium independent relaxation) in all rat aortic rings that did not differ statistically between groups. CONCLUSION: Astragalus has salutary effects on impaired endothelial dysfunction in the context of obesity.

[The protective effects of Radix Astragali and Rhizoma Ligustici chuanxiong on endothelial dysfunction in type 2 diabetic patients with microalbuminuria].

OBJECTIVE: To evaluate the effects of traditional Chinese complex prescription of Radix Astragali and Rhizoma Ligustici Chuanxiong on urinary albumin excretion (UAE) and vascular endothelial dysfunction in type 2 diabetic patients with microalbuminuria. METHODS: Twenty-one type 2 diabetic patients with microalbuminuria were involved in this before-after study by individual informed consent. Each of the eligible subjects was given the decoction of Radix Astragali and Rhizoma Ligustici Chuanxiong per os 150 ml q.d. for six months. The following examinations were performed at baseline and after treatment: (1) high-resolution ultrasonography to measure the diameter changes of brachial artery in response to reactive hyperemia (endothelium-dependent) and on administration of glyceryl trinitrate (endothelium-independent); (2) high resolution ultrasonography to measure combined intima-media thickness (IMT) of common carotid arteries (CCA); (3) fasting plasma plasminogen activator inhibitor type 1 (PAI-1) activity, C reactive protein (CRP) and malonic aldehyde(MDA) concentration. RESULTS: The patients had impaired endothelial dependent vasodilation (EDV), elevated plasma PAI-1 activity and increased CRP and MDA concentration at baseline. After six months treatment with Radix Astragali and Rhizoma Ligustici Chuanxiong, their urinary albumin-to- creatinine ratio decreased from (86.5 +/- 53.9) microg/mg to (55.05 +/- 51.67) microg/mg (P=0.002). The EDV was improved at the end of the treatment (baseline: 7.49 +/- 2.98%, after treatment: 12.73 +/- 5.36%, P=0.001). Meanwhile, the activity of PAI-1 and the levels of MDA and CRP were significantly decreased CPAI-1: (83.49 +/- 5.11) X 10(-2) AU/ml vs. (79.7 +/- 7.8) x 10(-2) AU/ml, P=0.015; MDA: (3.20 +/- 1.13) nmol/L vs. (2.09 +/- 0.71) nmol/L, P=0.000; CRP: (7.04 +/- 2.64) mg/ L vs. (1.58 +/- 0.69) mg/L, P=0.000]. But no significant changes of the CCA IMT and endothelial independent vasodilation (EIV) were observed. Partial correlated analysis showed that MDA concentration was negatively correlated with EDV (r=-0.3736, P = 0.018). Correlated analysis also showed that CRP was negatively correlated with EDV (r=-0.348, P=0.028). CONCLUSION: Radix Astragali and Rhizoma Ligustici Chuanxiong compound medication may decrease urinary albumin excretion and improve endothelial dysfunction in type 2 diabetic patients with microalbuminuria. The mechanism may relate with the therapeutic effects of Radix Astragali and Rhizoma Ligustici Chuanxiong on anti-inflammation, anti-oxidation and alleviation of the hypo-fibrinolytic/pro-thrombotic state.