Investigation of the Effects and Mechanisms of Mai Tong Formula on Lower Limb Macroangiopathy in a Spontaneous Diabetic Rat Model.

A new Chinese herbal formula called Mai Tong Formulae (MTF) has recently been used to treat lower limb macroangiopathy in type 2 diabetes mellitus (T2DM) patients. In this study, we investigated the effect of MTF on lower limb macroangiopathy in a spontaneous diabetic rat model (GK rats). We found that MTF treatment significantly reduced serum fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), IL6, and VEGF and increased serum insulin in this model. Histological and ultrastructural observations showed that MTF treatment significantly reduced vascular endothelial cell shedding and improved endothelium injuries. We further detect proteome alteration following MTF treatment. 25 differential proteins (DPs) abnormally expressed in GK rats were normalized by MTF treatment. These DPs significantly are enriched in biological processes and pathways that regulate muscle contraction and cGMP-PKG signaling pathway and so on. Additional protein-protein interaction (PPI) network analyses of the DPs showed that Fasn and Prkar2a are involved in the AMPK signaling pathway, and Gnas, Myh11, and Myh6 are involved in vascular smooth muscle contraction; these 5 DPs were validated by Western blotting. These results indicate that MTF treatment effectively treats lower limb macroangiopathy by regulating key proteins involved in AMPK signaling pathway and vascular smooth muscle contraction.

Pycnogenol® and Centella Asiatica for asymptomatic atherosclerosis progression.

AIM: The aim of the study was to evaluate the effect of the nutritional supplements Pycnogenol and TECA (total triterpenic fraction of Centella Asiatica) on atherosclerosis progression in low-risk asymptomatic subjects with carotid or femoral non-stenosing plaques. METHODS: This was an observational pilot substudy of the San Valentino epidemiological cardiovascular study. The study included 1363 subjects aged 45-60 without any conventional risk factors who had non stenosing atherosclerotic plaques (<50%) in at least one carotid or common femoral bifurcation, allocated into 6 groups: Group 1 (CONTROLS): management was based on education, exercise, diet and lifestyle changes. This same management plan was used in all groups; Group 2 Pycnogenol 50 mg/day; Group 3 Pycnogenol 100 mg/day; Group 4 Aspirin 100 mg/day or Ticlopidine 250 mg/day if intolerant to aspirin; Group 5 Aspirin 100 mg/day and Pycnogenol 100 mg/day; Group 6 Pycnogenol 100 mg/day plus TECA (total triterpenic fraction of Centella Asiatica) 100 mg/day. There was a six monthly follow-up up to 30 months. Plaque progression was assessed using the ultrasonic arterial score based on the arterial wall morphology and the number of plaques that progressed from the non-stenotic to the stenotic group. A secondary endpoint was to evaluate the changes in oxidative stress at baseline and at 30 months. RESULTS: The ultrasonic score increased significantly in groups 1, 2 and 4 but not in groups 3, 5 and 6 suggesting a beneficial effect of Pycnogenol 100 mg. The percentage of plaques that progressed from class IV to class V was 8.4% in group 2, 5.3% in group 3, 4% in group 5 and 1.1% in group 6 (P<0.0001) compared with 16.6% in group 4 (aspirin) and 21.3% in the control group suggesting a beneficial effect of Pycnogenol. The lowest rate of progression was in group 6 (Pycnogenol plus TECA). At 30 months, the oxidative stress in all the Pycnogenol groups was less than in the control group. The oxidative stress was lower in the Pycnogenol 100 mg group than the Pycnogenol 50 mg group (P<0.0001). In the combined group of Pycnogenol and TECA the oxidative stress was less than the Pycnogenol alone (P<0.001). CONCLUSION: Pycnogenol and the combination of Pycnogenol+TECA appear to reduce the progression of subclinical arterial lesions in low-risk asymptomatic subjects. The reduction in plaque progression was associated with a reduction in oxidative stress. The results justify a large randomized controlled study to demonstrate the efficacy of the combined Pycnogenol and TECA prophylactic therapy in subclinical atherosclerosis.

[Clinical study of acoustic densitometry technique in detecting atherosclerotic plaque].

OBJECTIVE: To investigate the effect of Quyu Xiaoban Capsule (QYXB) on the regressive treatment of atherosclerosis (AS) with acoustic densitometry (AD) technique. METHODS: Eighty patients with AS were randomly divided into two groups, trial group was treated with QYXB and conventional medicine, and control group was treated with conventional medicine alone. Normal arterial wall and different types of atherosclerotic plaques were detected with AD technique before treatment and 10 months later. RESULTS: The corrected averages in intimal echo intensity (AIIc%) were elevated in both groups but without significant difference, AIIc% of fatty plaques were increased in both groups and the value after treatment was significantly higher than that of pre-treatment in the trial group (68.12 +/- 5.54 vs 61.43 +/- 5.37, P < 0.05). The increment rate of AIIc% in trial group was significantly higher than that in control group (10.9 +/- 5.1% vs 2.5 +/- 5.5%, P < 0.05). CONCLUSION: QYXB can stabilize the atherosclerotic plaque by increasing its acoustic density. Acoustic densitometry technique can differentiate the different histological plaques and monitor the histological changes of plaques during treatment.

Inhibitory effect of a novel orally active GP IIb/IIIa inhibitor, SC-54684A on intimal thickening in the guinea pig femoral artery.

The inhibitory effect of a novel orally active platelet membrane glycoprotein receptor complex IIb/IIIa (GP IIb/IIIa) inhibitor, SC-54684A is studied on intimal thickening in the guinea pig femoral artery. A segment of the femoral artery was occluded by a platelet-rich thrombus induced by photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after successful thrombolysis by tissue-type plasminogen activator, intimal thickening occurred at the irradiated site. SC-54684A (30 mg/kg), administered 2 h before photochemical reaction, significantly (P < 0.05) prolonged the time to occlusion of the femoral artery; in this respect aspirin (100 mg/kg) was ineffective. A combination of SC-54684A and recombinant tissue-type plasminogen activator (rt-PA) increased the frequency of reopening and significantly (P < 0.05) prolonged the duration of reflow compared with rt-PA alone. Further, SC-54684A administered orally twice a day for 3 weeks significantly (P < 0.05) inhibited intimal thickening but aspirin, administered orally once a day for 3 weeks, was ineffective. Scanning electron microscopy revealed extensive platelet adhesion and aggregation on the denuded vessel walls in the untreated group 24 h after successful thrombolysis. In separate experiments, SC-54684A markedly inhibited platelet aggregation ex-vivo. Inhibition of platelet adhesion and aggregation at the site of endothelial injury by SC-54684A (via GPIIb/IIIa inhibition) may account for its inhibitory effect on intimal thickening.

Ultrastructural study of hypervitaminosis D induced arterial calcification in Wistar rats.

Hypervitaminosis D produces extensive vascular alterations which are similar to Monckeberg's calcinosis. The present study was undertaken to examine early changes in vascular ultrastructure of rats receiving tap water supplemented with either calcium chloride or a relatively low dosage of irradiated ergocalciferol ad libitum for 21 days. Untreated rats received normal tap water ad libitum. A significant increase in serum calcium levels was obtained in hypervitaminosis D treated rats. Calcium deposits were seen near the internal elastic lamina, within new elastic elements and around degenerating smooth muscle cell fragments in the extracellular organic matrix of hypervitaminosis D treated rats. Calcium deposits were not detected in vascular sections from untreated rats or those receiving calcium chloride. A complex pathogenesis of vascular lesions produced by hypervitaminosis is suggested. One possible pathogenic mechanism for calcification of elastic matrix may be via altered microfibrils. Our data support this hypothesis and indicate that much lower levels of vitamin D administration, compared to other reports, produce considerable vascular calcinosis in this experimental preparation. Several hypotheses regarding possible mechanisms of pathologic calcification are discussed.