Panax quinquefolius saponin inhibits vascular smooth muscle cell calcification via activation of nuclear factor-erythroid 2-related factor 2.

BACKGROUND: Panax quinquefolius saponin (PQS) is the main active component of Panax quinquefolius. Emerging evidence suggests that PQS exerts beneficial effects against cardiovascular diseases. However, the role and mechanism of PQS in vascular calcification are not unclear. The present study investigated the effects of PQS on the calcification of vascular smooth muscle cell (VSMCs). METHODS: The present study used calcification medium containing 3 mM inorganic phosphate (Pi) to induce rat VSMCs calcification. We investigated the effects of PQS on VSMCs calcification using alizarin red staining and alkaline phosphatase (ALP) activity assays. The intracellular reactive oxygen species (ROS) levels and the transcriptional activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined. The mRNA and protein expression levels of Nrf2, the antioxidant gene heme oxygenase-1 (HO-1), osteogenic markers, including runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), and Kelch-like ECH-associated protein 1 (Keap1) were also measured. RESULTS: Treatment with Pi significantly increased intracellular calcium deposition and ALP activity, which were suppressed by PQS in a concentration-dependent manner. During VSMCs calcification, PQS inhibited the mRNA and protein expression of Runx2 and BMP2. PQS treatment reduced intracellular ROS production and significantly upregulated Nrf2 transcriptional activity and the expression of Nrf2 and its target antioxidant gene HO-1. PQS suppressed the Pi-induced protein expression of Keap1, which is an endogenous inhibitor of Nrf2. Keap1 siRNA treatment induced Nrf2 expression and downregulated Runx2 expression in the presence of Pi and PQS. CONCLUSION: Taken together, these findings suggest that PQS could effectively inhibit VSMCs calcification by ameliorating oxidative stress and regulating osteogenic genes via the promotion of Nrf2 expression.

Insulin-like growth factor-binding protein-1 (IGFBP-1) in goldfish, Carassius auratus: molecular cloning, tissue expression, and mRNA expression responses to periprandial changes and cadmium exposure.

In this study, the cDNA encoding insulin-like growth factor-binding protein-1 (IGFBP-1) was cloned from the liver of goldfish (Carassius auratus). The obtained goldfish IGFBP-1 cDNA sequence was 1037 bp in length and had an open reading frame of 789 bp encoding a predicted polypeptide of 262 amino acid residues. IGFBP-1 transcript was detected in all tested central nervous and peripheral tissues. The relatively higher levels of IGFBP-1 mRNA were observed in the liver, gill, kidney, heart, spleen, fat and testis, while the lower levels were found in all different regions of brain, muscle and intestine. In the skin, IGFBP-1 mRNA expression level was extremely low. The IGFBP-1 mRNA expression level in liver was significantly elevated after feeding. With cadmium exposure for 24 h, IGFBP-1 mRNA expression levels in spleen and liver were significantly increased at different cadmium concentrations ranging from 0.5 to 10 ppm. The results in this study provided the data regarding molecular characteristics and expression patterns of IGFBP-1 in goldfish and showed that the expression of IGFBP-1 mRNA might be associated with metabolic status and heavy metal stress and regulated by metabolic factors and cadmium in fish.

Rehmannia glutinosa extract activates endothelial progenitor cells in a rat model of myocardial infarction through a SDF-1 α/CXCR4 cascade.

OBJECTIVES: Endothelial progenitor cells (EPCs) can be used to repair tissues after myocardial infarction (MI) but EPC activators have adverse reactions. Rehmannia glutinosa is a herb used in traditional Chinese medicine, which can promote bone-marrow proliferation and protect the ischemic myocardium. We investigated the effects of Rehmannia glutinosa extract (RGE) on EPCs in a rat model of MI. METHODS: A total of 120 male Wistar rats were randomized to 2 groups (n=60 each) for treatment: high-dose RGE (1.5 g·kg(-1)·day(-1) orally) for 8 weeks, then left anterior descending coronary artery ligation, mock surgery or no treatment, then RGE orally for 4 weeks; or normal saline (NS) as the above protocol. The infarct region of the left ventricle was assessed by serial sectioning and morphology. EPCs were evaluated by number and function. Protein and mRNA levels of CD133, vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-X-C motif receptor 4 (CXCR4), stromal cell-derived factor-1α (SDF-1α) were measured by immunohistochemistry, Western blot and quantitative PCR analysis. RESULTS: RGE significantly improved left ventricular function, decreased the ischemic area and the apoptotic index in the infarct myocardium, also decreased the concentration of serum cardiac troponin T and brain natriuretic peptide at the chronic stage after MI (from week 2 to week 4). RGE increased EPC number, proliferation, migration and tube-formation capacity. It was able to up-regulate the expression of angiogenesis-associated ligand/receptor, including CD133, VEGFR2 and SDF-1α/CXCR4. In vitro, the effect of RGE on SDF-1α/CXCR4 cascade was reversed by the CXCR4 specific antagonist AMD3100. CONCLUSION: RGE may enhance the mobilization, migration and therapeutic angiogenesis of EPCs after MI by activating the SDF-1α/CXCR4 cascade.

Sulfotanshinone Sodium Injection could decrease fibrinogen level and improve clinical outcomes in patients with unstable angina pectoris.

We randomly divided 100 unstable angina pectoris (UAP) patients into two groups: the trial group received Sulfotanshinone Sodium Injection (SSI) 60 mg combined with a loading dose of 300 mg aspirin and a maintenance dose of 100 mg of aspirin plus baseline therapy, and the control group received the same doses of aspirin and baseline therapy. 94 patients completed treatment. After 4 weeks' medication, the severity of angina pectoris improved in both groups, with a significant improvement in total effective rate in the trial group but no difference in the total effective rate of improvement seen on ECG. Compared with baseline level, FIB level after treatment decreased significantly in both groups but to a greater extent in the trial group. Similar changes in DD levels were observed in both groups. With a background of aspirin and baseline therapy, SSI can significantly attenuate angina pectoris attacks in patients with UAP which may be associated with the decreased level of FIB.

Herba Epimedii water extract elevates estrogen level and improves lipid metabolism in postmenopausal women.

Hormone replacement therapy (HRT) can ameliorate lipid metabolism after menopause, but it is not suitable for long-term use because of serious side effects. Herba Epimedii is a widely used herbal medicine in many Asian countries, it potentially treats menopausal syndrome and its complications with few side effects and good curative effects. The study aimed to evaluate the effects of Herba Epimedii water extract on blood lipid and sex hormone levels. Ninety subjects were randomly divided into two groups: a trial group which received Herba Epimedii water extract and a control group which was administered an equal amount of water placebo. At the baseline and after 6 months of medication, serum estradiol (E(2)), progesterone (P), testosterone (T), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) concentrations were measured. The results indicated that Herba Epimedii water extract decreased the TC and TG levels (p < 0.01). Furthermore, Herba Epimedii water extract significantly increased the serum level of E(2) (p < 0.01) compared with the pre-treatment level. In conclusion, Herba Epimedii water extract produces its beneficial actions in postmenopausal women.

Effects of Bulbus allii macrostemi on clinical outcomes and oxidized low-density lipoprotein and plasminogen in unstable angina/non-ST-segment elevation myocardial infarction patients.

Unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) is associated with an increased risk of cardiac death and an efficacious drug with few side effects is necessary. The study aimed to evaluate the effects of Bulbus allii macrostemi (B. macrostemi) on UA/NSTEMI patients as well as to elucidate possible mechanisms. 79 patients were randomly divided into two groups: the trial group received B. macrostemi plus baseline therapy, the control group was given placebo plus baseline therapy. The trial lasted 8 weeks. The evaluation involved main clinical symptoms, changes of electrocardiogram and biochemical examination. After treatment, the trial group showed more significant improvement on clinical manifestation. The plasma oxidized low-density lipoprotein (ox-LDL) level decreased significantly in the trial group (p < 0.01); the plasminogen activator inhibitor-1 (PAI-1) level decreased in both groups and it decreased more significantly in the trial group (p < 0.01). In contrast, the activity of plasminogen (PLG) increased in both groups and the change was more marked in the trial group (p < 0.01). The results suggested that B. macrostemi combined with baseline therapy could improve clinical symptoms of UA/NSTEMI patients by decreasing the ox-LDL and PAI-1 levels and enhancing the activity of PLG.

Aqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulation.

The study evaluated the effect of the traditional Chinese medicine rhubarb on the stability of atherosclerotic plaque. Atherosclerotic lesions were induced in rabbits through balloon injury with a high-cholesterol diet and then were divided into a control group, a rhubarb group and a simvastatin group. At week 24 recombinant-p53 adenoviruses were locally delivered to the atherosclerotic plaques. At week 26 plaque rupture was triggered by the intra-arterial Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathologic, immunohistochemical and gene expression studies were performed. The results showed that the incidence of plaque rupture in the rhubarb group and the simvastatin group was significantly lower than that in the control group (42.86% and 35.71% versus 80.00%, both p < 0.05). Serum TC, LDL-C (p < 0.05-0.01), IMT (both p < 0.01), PA (both p < 0.01), PB (%) (both p < 0.01) and the mRNA and protein expressions of TLR2, TLR4 and NF-kappaB (p < 0.05, 0.01, respectively) in the rhubarb group and the simvastatin group were significantly lower than those in the control group. In contrast, AIIc% (both p < 0.05) in the two treatment groups were significantly higher than those in the control group. These results suggest that rhubarb has antiatherosclerotic and plaque-stabilizing properties due to antiinflammation and lipid-lowering effects.

Treatment with rhubarb improves brachial artery endothelial function in patients with atherosclerosis: a randomized, double-blind, placebo-controlled clinical trial.

Rhubarb has been used to decrease plasma cholesterol levels and reduce vascular endothelial cellular damage in recent years. However, it is not known whether reported lipid-lowering effects are associated with the improvement of endothelial function. This work aimed to elucidate the therapeutic effects of rhubarb on serum lipids and brachial artery endothelial function, as well as to investigate the relationship between them. One hundred and three patients with atherosclerosis were randomly divided into two groups: patients in the control and the trial group received a placebo and rhubarb, respectively, in addition to the 6 month baseline therapy. Serum lipids and brachial artery endothelial functions were measured in all patients before and after treatment. A total of 83 patients completed the 6-month follow-up protocol. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the trial group decreased significantly and LDL-C was significantly lower than that in the control group. Flow-mediated dilation (FMD) in the trial group was significantly higher after treatment in comparison to the baseline and to the control group. Improvement in FMD correlated with the decreased magnitude of TC and LDL-C levels. The results obtained appeared to confirm that rhubarb significantly improves endothelial function mainly due to lipid-lowering effects in patients with atherosclerosis.