Effects of an ethanolic extract of mulberry fruit on blood pressure and vascular remodeling in spontaneous hypertensive rats.

Mulberry (Morus alba) has been used in traditional oriental medicine since ages. Recently, it has been reported that mulberry produces hypotensive effects through the eNOS signaling pathway. However, the mechanism underlying the hypotensive effects of mulberry is not entirely clear. Moreover, the effects of mulberry on vascular remodeling events such as hyperplasia, an important etiology in the pathogenesis of hypertension and arteriosclerosis, are also ambiguous. Here, we hypothesized that an ethanolic extract of mulberry fruit (EMF) has beneficial effects on vascular remodeling and produces hypotensive effects. The effects of a 6-week oral administration of EMF were examined in spontaneously hypertensive rats (SHRs). The animals were divided into four groups: normotensive control (Wistar Kyoto rats), non-treated SHR, low-dose (100 mg/kg) EMF-treated SHR, and high-dose (300 mg/kg) EMF-treated SHR. Our results showed that the EMF-diet normalizes hypertension in SHRs in a dose-dependent manner, by preventing smooth muscle proliferation, thickening of the tunica media, and vascular hyper-reactivity. The endothelial functions were not substantially affected by the EMF diet in our experimental setting. In conclusion, we suggest that the mulberry fruit could act as a food supplement for reducing blood pressure in hypertensive subjects through its effects on smooth muscle proliferation and vascular contractility.

Transplantation of Bone Marrow Mesenchymal Stem Cells Prevents Radiation-Induced Artery Injury by Suppressing Oxidative Stress and Inflammation.

The present study aims to explore the protective effect of human bone marrow mesenchymal stem cells (hBMSCs) on radiation-induced aortic injury (RIAI). hBMSCs were isolated and cultured from human bone marrow. Male C57/BL mice were irradiated with a dose of 18-Gy 6MV X-ray and randomly treated with either vehicle or hBMSCs through tail vein injection with a dose of 103 or 104 cells/g of body weight (low or high dose of hBMSCs) within 24 h. Aortic inflammation, oxidative stress, and vascular remodeling were assessed by immunohistochemical staining at 3, 7, 14, 28, and 84 days after irradiation. The results revealed irradiation caused aortic cell apoptosis and fibrotic remodeling indicated by aortic thickening, collagen accumulation, and increased expression of profibrotic cytokines (CTGF and TGF-ß). Further investigation showed that irradiation resulted in elevated expression of inflammation-related molecules (TNF-α and ICAM-1) and oxidative stress indicators (4-HNE and 3-NT). Both of the low and high doses of hBMSCs alleviated the above irradiation-induced pathological changes and elevated the antioxidant enzyme expression of HO-1 and catalase in the aorta. The high dose even showed a better protective effect. In conclusion, hBMSCs provide significant protection against RIAI possibly through inhibition of aortic oxidative stress and inflammation. Therefore, hBMSCs can be used as a potential therapy to treat RIAI.

Thalidomide treatment prevents chronic graft rejection after aortic transplantation in rats - an experimental study.

Cardiac allograft vasculopathy (CAV) affects approximately 30% of cardiac transplant patients at 5 years post-transplantation. To date, there are few CAV treatment or prevention options, none of which are highly effective. The aim of the study was to investigate the effect of thalidomide on the development of CAV. The effect of thalidomide treatment on chronic rejection was assessed in rat orthotopic aortic transplants in allogeneic F344 or syngeneic Lew rats (n = 6 per group). Animals were left untreated or received thalidomide for 30 days post-transplant, and evidence of graft CAV was determined by histology (trichrome and immunohistochemistry) and intragraft cytokine measurements. Animals that received thalidomide treatment post-transplant showed markedly reduced luminal obliteration, with concomitant rescue of smooth muscle cells (SMCs) in the aortic media of grafts. Thalidomide counteracted neointimal hyperplasia by preventing dedifferentiation of vascular SMCs. Measurement of intragraft cytokine levels after thalidomide treatment revealed downregulation of matrix metalloproteinase 8 and monocyte chemotactic protein 1, cytokines involved in tissue remodelling and inflammation, respectively. Importantly, no negative side effects of thalidomide were observed. Thalidomide treatment prevents CAV development in a rodent model and is therefore potentially useful in clinical applications to prevent post-transplant heart rejection.

Anti-atherosclerotic effect of geniposidic acid in a rabbit model and related cellular mechanisms.

CONTEXT: Geniposidic acid, one of the main active ingredients in Gardenia jasminoides J. Ellis (Rubiaceae), may also possess important pharmacological activities for cardiovascular disorders similar to other derivatives, such as geniposide. OBJECTIVE: To evaluate its anti-atherosclerosis (anti-AS) effect, the related pharmacological activities and possible cellular mechanisms were studied. MATERIALS AND METHODS: Thirty rabbits were randomly divided into normal control group, model control group, and geniposidic acid subgroups. In the AS model, its effects on the intima/media thickness ratio and aortic morphology were observed. In the study of primary cultured endothelial cells (ECs) and human umbilical artery smooth muscle cells (HUASMCs), its activities on both ECs and HUASMCs proliferation, HUASMCs' migration were also studied. RESULTS: Compared with the model control group, the plaque area, intima/media thickness ratio, and intimal foam cells number in geniposidic acid (80, 160, and 240 mg/kg) subgroups were significantly improved (p < 0.05). By HE staining, the activities of geniposidic acid on relieving ECs shedding and improving aortic morphology disorders were also demonstrated. From the results of CCK-8 testing, only 100 µg/ml geniposidic acid performed significant inhibition on SMC proliferation. The relative IC50 of geniposidic acid on SMC inhibition was 87.73 µg/ml. Geniposide acid also showed promotion effect on ECs proliferation, and the related ED50 of geniposidic acid was 86.05 µg/ml. Besides, only 50 and 100 µg/ml geniposidic acid showed obvious inhibition on SMC migration from the upper chamber (p < 0.05). DISCUSSION AND CONCLUSION: The effects of geniposidic acid on protecting vascular endothelium and reversing plaque formation in an atherosclerotic model were demonstrated.

Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

Anti-diabetic atherosclerosis effect of Prunella vulgaris in db/db mice with type 2 diabetes.

Diabetes mellitus is the leading cause of vascular complications such as atherosclerosis. This study was designed to investigate whether Prunella vulgaris (APV) would inhibit diabetic atherosclerosis in db/db mice with type 2 diabetes. The db/db mice were treated with high fat/high cholesterol (HFHC) diet and an aqueous extract of APV (100 and 200 mg/kg/day) for eight weeks to examine the long-term effect on metabolic abnormalities and diabetic atherosclerosis. APV treatment markedly lowered blood glucose and systolic blood pressure. The db/db mice experienced an increase in blood urea nitrogen as well as a decrease of creatinine clearance, the latter of which was restored by treatment with APV. Treatment with APV markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol and also increased the HDL-cholesterol. In addition, malondialdehyde and TGF-ß1 were decreased by treatment of APV. On the other hand, total NO level was decreased in db/db mice. However, the NO level was increased by treatment with APV, suggesting an association with vascular dysfunction. Vascular relaxation of aortic rings by acetylcholine or SNP-inducement was ameliorated by APV in a dose-dependent manner. Damage of vascular intima and hypertrophic of media were observed in db/db mice; however its dysfunction was improved by the treatment of APV. APV treatment significantly reduced the aortic expressions of ICAM-1, VCAM-1, ET-1, and nitrotyrosine. Furthermore, expression of eNOS in aortic was remarkably increased by APV treatment. Taken together, APV suppressed hyperglycemia and diabetic vascular dysfunction in HFHC diet-db/db mice. The present data suggest that Prunella vulgaris may prevent development of diabetic atherosclerosis.

Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a rare disorder that without treatment is progressive and often fatal within 3 years. The treatment of PH involves the use of a diverse group of drugs and lung transplantation. Although nitrite was once thought to be an inactive metabolite of endothelial-derived nitric oxide (NO), there is increasing evidence that nitrite may be useful in the treatment of PH, but the mechanism by which nitrite exerts its beneficial effect remains uncertain. The purpose of this study was to investigate the effect of chronic sodium nitrite treatment in a PH model in the rat. Following induction of PH with a single injection of monocrotaline, 60 mg; daily ip injections of sodium nitrite (3mg/kg) starting on day 14 and continuing for 21 days, resulted in a significantly lower pulmonary arterial pressure on day 35 when compared to values in untreated animals with monocrotaline-induced PH. In monocrotaline-treated rats, daily treatment with ip nitrite injections for 21 days decreased right ventricular mass and pathologic changes in small pulmonary arteries. Nitrite therapy did not change systemic arterial pressure or cardiac output when values were measured on day 35. The decreases in pulmonary arterial pressure in response to iv injections of sodium nitroprusside, sodium nitrite, and BAY 41-8543 were not different in rats with monocrotaline-induced pulmonary hypertension and rats with chronic nitrite therapy when compared to responses in animals in which pulmonary arterial pressure was increased with U46619. These findings are consistent with the hypothesis that the mechanisms that convert nitrite to vasoactive NO, activate soluble guanylyl cyclase and mediate the vasodilator response to NO or an NO derivative are not impaired. The present data are consistent with the results of a previous study in monocrotaline-induced PH in which systemic arterial pressure and cardiac output were not evaluated and are consistent with the hypothesis that nitrite is effective in the treatment of monocrotaline-induced PH in the rodent.

Salviae Miltiorrhizae Radix and Puerariae Lobatae Radix herbal formula mediates anti-atherosclerosis by modulating key atherogenic events both in vascular smooth muscle cells and endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Salviae Miltiorrhizae Radix (Danshen) and Puerariae Lobatae Radix (Gegen) are principal herbs have long been used in combination for treating cardiovascular disease. AIMS OF STUDY: Danshen and Gegen in the ratio of 7:3 (DGW) have significantly reduced the carotid intimal-media thickening (IMT) in patients in our previous clinical study. In the present study, we have demonstrated the mechanisms on IMT reduction by investigating its key processes on both vascular smooth muscle cell (vSMC) and endothelial cells. MATERIALS AND METHODS: The anti-proliferative effects of DGW on platelet-derived growth factor (PDGF) induced vSMC proliferation were studied by cell proliferation, cell cycle distribution, p-ERK and cyclin D expression level. The anti-migratory effect of DGW was investigated by using transwell apparatus. For human umbilical endothelial cells (HUVEC), the inhibitory effects of DGW on TNF-alpha induced cell adhesion, cell adhesion molecules expression, MCP-1 and IL-6 production were investigated. RESULTS: DGW significantly inhibited A7r5 proliferation and exhibited G1/S cell cycle arrest by suppressing both p-ERK and cyclin D expression. Moreover, DGW showed anti-migratory effect against PDGF-induced A7r5 migration. In addition, DGW inhibited the cell adhesion as well as the expression of ICAM-1 and VCAM-1, the production of MCP-1 but not IL-6 in TNF-α stimulated HUVECs. CONCLUSIONS: Our study provided strong scientific evidence on IMT reduction in patients by modulating the key atherogenic events in both vSMC and endothelial cells.

Hypotensive, hypolipidemic, and vascular protective effects of Morus alba L. in rats fed an atherogenic diet.

Morus alba L. has been used in traditional Chinese medicine and almost all parts of this plant are useful in cardiovascular, liver and spleen disorders. The present study was designed to investigate the inhibitory effect of a water extract from Morus alba L. (WMA) on vascular dysfunction in rat models fed a high fat and high cholesterol diet. Male rats were fed an atherogenic diet consisting of food with 7.5% cocoa butter and 1.25% cholesterol, with or without 100 or 200 mg/day/kg WMA, for 14 weeks. Chronic treatment with low (100 mg/kg/day) or high (200 mg/day/kg) doses of WMA markedly attenuated hypertension and the impairments of acetylcholine-induced relaxation of aortic rings in rats fed an atherogenic diet. WMA reduced intima/media thickness in rats fed an atherogenic diet. WMA improved plasma levels of triglyceride (TG) and augmented plasma levels of high-density lipoprotein (HDL) and plasma low-density lipoprotein (LDL), but did not affect blood glucose levels. Interestingly, WMA suppressed increased cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) expression in the aorta. Taken together, these results suggested that Morus alba L. could improve an atherogenic diet-induced hypertension, hyperlipidemia, and vascular dysfunction through inhibition of cell adhesion molecules expression and induction of vascular relaxation.

Effect of tongxinluo on vasoconstriction induced by the chronic injury of the adventitia in the rat carotid artery.

OBJECTIVE: Tongxinluo (TXL) is a traditional Chinese medicine that is developed on the meridian theory of traditional Chinese medicine, with the function of alleviating the angina. The present study was undertaken to explore the molecular mechanism of TXL in treating the pectoris angina through observing the effectiveness of TXL superfine powder on the vasoconstriction and the activation of RhoA/Rho-kinase pathway induced by the injury of the adventitia. METHODS: 36 male Wistar Kyoto rats were assigned to 3 treatments (n=12): vehicle, TXL (400 mg kg(-1) day(-1)) and fasudil (15 mg kg(-1) day(-1)). After 1 week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for 1 week. Blood flow and vascular reactivity to serotonin were determined 1 week after injurying, the both sides of carotids were harvested for morphometry, Western blotting analysis and RT-PCR analysis. RESULTS: Adventitia injury leaded to histological changes of vasoconstriction with the lumen cross-sectional area of 44.7% (p<0.001) decreasing and the media diameter of 62.31% (p<0.001) increasing, accompanying by the reduction of the blood flow and the increase of vascular reactivity sensitivity to serotonin. Treatment with both TXL superfine powder and fasudil can prevent the development of vasoconstriction, improve the carotid blood flow and normalize the vascular hypersensitivity to serotonin. Adventitia injuring of the rat carotid increased the expression of Rho-kinase mRNA and p-MYPT1(Thr696) protein by 1.78-fold (p<0.05) and >2-fold respectively (p<0.05). TXL reduced the expression of Rho-kinase mRNA and p-MYPT1(Thr696) protein by 54.2% (p<0.05) and 57.1% (p<0.05) respectively in collared arteries. Fasudil restrained the p-MYPT1(Thr696) protein expression by 63.8% (p<0.05) in collared arteries, did not affect the collar-induced the increase of Rho-kinase mRNA expression (p>0.05). CONCLUSIONS: Treatment with TXL, similar to that with fasudil, can effectively prevent collar-induced vasoconstriction and vascular hyperreactivity to serotonin through inhibiting the RhoA/Rho-kinase pathway.

Morphometric analysis of the influence of selenium over vasospastic femoral artery in rats.

BACKGROUND: Cerebral vasospasm (CV) is the leading cause of morbidity and mortality occurring after subarachnoid hemorrhage (SAH). Etiopathogenesis of CV is multifactorial. Selenium is the cofactor of the glutathione peroxidase (GSH-Px) enzyme which is a very important defense mechanism against antioxidants. According to the literature, oxidants are known to play a remarkable role in the pathogenesis of vasospasm occurring after SAH. Therefore, many studies have been conducted with antioxidant agents, based on the theory that elevated activity of GSH-Px enzyme might prevent the development of CV after SAH. Majority of those studies reported positive results. However, as a result of our literature review, we came across no study which involves the investigation of the role of selenium alone in the prevention of CV after SAH. In our study, we aim to find the answer to the following question: "Can selenium alone prevent cerebral vasospasm following SAH at early stage?" METHODS: We used the "rat femoral artery vasospasm model" of Okada et al. as the vasospasm model of our study. First, rats were divided into three groups: group 1 (n = 8), control group; group 2 (n = 8), vasospasm group; and group 3 (n = 8), vasospasm + selenium group. Statistical comparison of groups 1 and 2 revealed significant thickening in the vascular wall and a decrease in the lumen diameter in group 2, compared with group 1. Statistical comparison of the vascular lumen diameters of groups 1 and 3 showed no significant difference, whereas the comparison of mean vascular wall thickness displayed a significant increase in group 3. Moreover, statistical comparison of groups 2 and 3 regarding vascular lumen diameters showed a significant decrease in group 2, whereas group 3 displayed a significant decrease in terms of vascular wall thickness. CONCLUSION: According to the results of our study, selenium morphometrically prevents the development of peripheral vasospasms.

Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium. RESEARCH DESIGN AND METHODS: A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 microg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated. RESULTS: After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects. CONCLUSIONS: Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.

Effects of five-year intensive multifactorial intervention on the serum amyloid A and macroangiopathy in patients with short-duration type 2 diabetes mellitus.

BACKGROUND: A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A (SAA) levels and the incidence of atherosclerosis (AS) in patients with short-duration type 2 diabetes mellitus (T2DM) without macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurrence of macroangiopathy. METHODS: Among 150 patients with short-duration T2DM, 75 were assigned to receive conventional outpatient treatment (conventional group) and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia, hypertension, dyslipidemia and received aspirin simultaneously (intensive group). RESULTS: Plasma SAA levels were higher in diabetic patients than those in healthy control subjects, and decreased obviously after intensive multifactorial intervention. The levels of SAA were positively correlated with body mass index (BMI), waist hip ratio (WHR), triglyceride (TG), high sensitive C-reactive protein (hs-CRP) and common carotid intima-media thickness (CC-IMT). The standard-reaching rates of glycemia, blood pressure and lipidemia were significantly higher in intensive group than those of conventional group. The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group. CONCLUSIONS: Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM. SAA might be one of the risk factors of T2DM combined with AS.

Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study.

OBJECTIVES: Our aim was to determine the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function. BACKGROUND: NA raises high-density lipoprotein cholesterol (HDL-C) and reduces low-density lipoprotein cholesterol and is widely used as an adjunct to statin therapy in patients with coronary artery disease. Although changes in plasma lipoproteins suggest potential benefit, there is limited evidence of the effects of NA on disease progression when added to contemporary statin treatment. METHODS: We performed a double-blind, randomized, placebo-controlled study of 2 g daily modified-release NA added to statin therapy in 71 patients with low HDL-C (<40 mg/dl) and either: 1) type 2 diabetes with coronary heart disease; or 2) carotid/peripheral atherosclerosis. The primary end point was the change in carotid artery wall area, quantified by magnetic resonance imaging, after 1 year. RESULTS: NA increased HDL-C by 23% and decreased low-density lipoprotein cholesterol by 19%. At 12 months, NA significantly reduced carotid wall area compared with placebo (adjusted treatment difference: -1.64 mm(2) [95% confidence interval: -3.12 to -0.16]; p = 0.03). Mean change in carotid wall area was -1.1 +/- 2.6 mm(2) for NA versus +1.2 +/- 3.0 mm(2) for placebo. In both the treatment and placebo groups, larger plaques were more prone to changes in size (r = 0.4, p = 0.04 for placebo, and r = -0.5, p = 0.02 for NA). CONCLUSIONS: In statin-treated patients with low HDL-C, high-dose modified-release NA, compared with placebo, significantly reduces carotid atherosclerosis within 12 months. (Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function; NCT00232531).

Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease.

This randomized, double-blind, parallel trial assessed the influence of pomegranate juice consumption on anterior and posterior carotid intima-media thickness (CIMT) progression rates in subjects at moderate risk for coronary heart disease. Subjects were men (45 to 74 years old) and women (55 to 74 years old) with > or =1 major coronary heart disease risk factor and baseline posterior wall CIMT 0.7 to 2.0 mm, without significant stenosis. Participants consumed 240 ml/day of pomegranate juice (n = 146) or a control beverage (n = 143) for up to 18 months. No significant difference in overall CIMT progression rate was observed between pomegranate juice and control treatments. In exploratory analyses, in subjects in the most adverse tertiles for baseline serum lipid peroxides, triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, TGs/HDL cholesterol, total cholesterol/HDL cholesterol, and apolipoprotein-B100, those in the pomegranate juice group had significantly less anterior wall and/or composite CIMT progression versus control subjects. In conclusion, these results suggest that in subjects at moderate coronary heart disease risk, pomegranate juice consumption had no significant effect on overall CIMT progression rate but may have slowed CIMT progression in subjects with increased oxidative stress and disturbances in the TG-rich lipoprotein/HDL axis.

The efficacy and tolerability of adjunctive alternative herbal medicine (Salvia miltiorrhiza and Pueraria lobata) on vascular function and structure in coronary patients.

BACKGROUND: Danshen and gegen (D&G) have long been used in treatment of angina and other cardiac symptoms in Chinese materia medica. Recent pharmacological studies suggest their therapeutic values. We aimed to evaluate the efficacy and safety of Salvia miltiorrhiza (danshen) and Pueraria lobata (gegen) in secondary prevention. METHODS: One hundred (100) consecutive coronary patients (mean age 58 +/- 8 years) were randomized to adjunctive treatment with D&G combination (3 g) or placebo (6 capsules) for 24 weeks in double-blind parallel fashion, followed by optional open-label D&G (1.5 g/day) for 6 more months. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured using ultrasound. RESULTS: Baseline characteristics were similar between the 2 groups. After 24 weeks and compared with baseline, there were no significant changes in blood pressures, blood hematological and biochemical profiles, or folate and homocysteine levels in both groups, but there was a mild decrease in low density lipoprotein (LDL) cholesterol in both groups (p < 0.05). Brachial FMD improved during D&G (p < 0.001) and less so during placebo treatment (p < 0.05), while improvement in carotid IMT was observed only in the D&G group (p < 0.05). After open-label D&G treatment for 6 more months (n = 45), further improvement in both brachial FMD (p < 0.0001) and carotid IMT (p < 0.0001) was observed. Eight (8) adverse events were reported-6 during placebo and 2 during D&G treatment-requiring treatment termination in 2 patients (on placebo). CONCLUSIONS: D&G adjunctive treatment in coronary patients was well tolerated and effective in improving vascular function and structure. These two herbs may become a novel agent for secondary prevention.

Role of folic acid in atherosclerosis after kidney transplant: a double-blind, randomized, placebo-controlled clinical trial.

OBJECTIVES: We investigated the effects of folic acid supplementation on plasma total homocysteine levels and carotid intima-media thickness after kidney transplant. MATERIALS AND METHODS: Sixty patients who had undergone a kidney transplant were studied in this double-blind, randomized, placebo-controlled clinical trial. Those subjects were randomized to receive either 5 mg/d of oral folic acid or an equivalent dosage of placebo. The main outcome variables were the plasma total homocysteine level and carotid intima-media thickness (determined via B-mode sonography) at baseline and 2, 4, and 6 months after kidney transplant. We used independent and paired sample t tests for data analysis. RESULTS: The mean age of the patients was 40.9 -/+ 10 years, and 32 of those subjects (58.2%) were men. In the control group, the plasma total homocysteine levels were 19 micromol/L at baseline, 18.7 micromol/L after 2 months, 19.3 micromol/L after 4 months, and 20 micromol/L after 6 months; and the carotid intima-media thickness measurements were 0.81 mm at baseline, 0.82 mm after 2 months, 0.84 mm after 4 months, and 0.85 mm after 6 months. In the folic acid group, the plasma total homocysteine levels were 18.5 micromol/L at baseline, 4.7 micromol/L after 2 months, 12.9 micromol/L after 4 months, and 10.9 micromol/L after 6 months; and the carotid intima-media thickness measurements were 0.73 mm at baseline, 0.73 mm after 2 months, 0.72 mm after 4 months, and 0.71 mm after 6 months. CONCLUSIONS: Folic acid supplementation reduces both the plasma total homocysteine level and carotid intima-media thickness shortly after kidney transplant.

Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats.

UNLABELLED: PREMISES AND OBJECTIVES: Antioxidant plays an important role in preventing the progression of diabetes mellitus (DM) complications. The aim of the present study was to investigate the effect of alpha lipoic acid (ALA) supplementation on plasma lipid, oxidative stress and vascular changes in diabetic rats. MATERIAL AND METHODS: Diabetes was induced by a single intravenous injection of streptozotocin (STZ) (50 mg/kg). The diabetic rats were divided into two groups: (i) supplemented group with ALA (100 mg/kg/day) and (ii) non-supplemented group without ALA. Non-diabetic rats (NDM) formed the control group, which received saline injection. RESULTS: Following eight weeks of supplementation, fasting blood glucose (FBG) and glycosylated hemoglobin (HBA1c) in ALA-supplemented rats was found to be significantly lower than the non-supplemented group. ALA-supplementation also improved dyslipidemia that occurred in diabetic rats. ALA-supplementation also significantly increased plasma superoxide dismutase (SOD) activity and vitamin C level as compared to the No Suppl group. The increase in plasma and aorta malondealdehyde + 4-hydroxynonenal (MDA + 4-HNE) levels were also inhibited and the levels of oxidative DNA damage of peripheral lymphocytes were significantly reduced. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats with ALA-supplementation reducing the changes in the vascular morphology. CONCLUSIONS: It is concluded that ALA has the potential in preventing the alteration of vascular morphology in diabetic rats probably through the improvement of glycemic status and dyslipidemia as well as its antioxidant activities.

The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis.

BACKGROUND: Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown. METHODS: We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B6 25 mg and vitamin B12 0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD. RESULTS: After a mean treatment period of 3.9 +/- 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 micromol/L, 95% CI 7.5 to 8.4 versus 11.8 micromol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 +/- 0.17 mm vitamins versus 0.83 +/- 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials. CONCLUSION: Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.