Sesamin and vitamin E ameliorate aortic endothelial dysfunction rats induced by D-galactose and aluminum trichloride via regula?tion of endothelial nitric oxide synthase and NAD(P)H oxidase 4 / 中国药理学与毒理学杂志

OBJECTIVE To observe the protective effect of sesamin (Ses) and vitamin E (Vit E) against aortic endothelial dysfunction in rats induced by D-galactose (D-gal) and aluminum trichloride (AlCl3), and explore its conceivable mechanisms. METHODS A model of aortic endothelial dysfunction rats was established by D-gal (180 mg · kg-1, ip) combined with AlCl3 (15 mg · kg-1, ig) for 84 d. Model rats were randomly divided into model, model+Vit E 10 mg·kg-1, model+Ses 160 mg·kg-1, and model+Ses 160 mg · kg-1+Vit E 10 mg · kg-1 groups. After 70 d of treatment with Ses and Vit E, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) were measured by tail cuff. The rats were anesthetized by sodium pentobarbital (30 mg·kg-1, ip). Thoracic aortas from the rats were removed and divided into two parts (3 mm in length). The relaxation of the aortic ring induced by acetylcholine (ACh) and sodium nitroprusside was measured. The primary pathologic changes in the aorta were observed by HE staining. Total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2) and nitric oxide (NO) in serum were measured by colorimetric analysis. The expression of endothelial nitric oxide synthase (eNOS) positive cells in the aorta were measured by immunohistochemistry. The expres?sions of eNOS and NAD(P)H oxidase 4 (NOX4) protein in the aortal were detected by Western blotting. RESULTS Compared with the model group, the relaxation response with increase in ACh concentra?tion (1×10-7-1×10-4 mol·L-1) was enhanced (P<0.01) in model+Ses+Vit E, SBP, DBP and MBP decreased (P<0.01), the serum T-AOC and NO level were increased (P<0.01), the serum H2O2 levels were reduced (P<0.01), the eNOS expression was increased (P<0.01) and NOX4 expression was reduced (P<0.01) in each treatment group. Compared with model+Ses, the SBP, DBP and MBP were lower (P<0.01 or P<0.05), the serum H2O2 level was lower (P<0.01), the serum NO level was increased (P<0.05), the eNOS expression level was higher (P<0.01) and the NOX4 expression level was reduced (P<0.05) in model+Ses+Vit E. Compared with the model+Vit E, the serum T-AOC and NO levels were increased (P<0.05), the serum H2O2 level was lower (P<0.01), eNOS expression was increased (P<0.01) and NOX4 expression was reduced (P<0.05) in model+Ses+Vit E group. CONCLUSION Ses and Vit E can ameliorate aortic endothelial dysfunction of rats induced by D-gal and AlCl3 via the regulation of eNOS and NOX4.

Effect of salvianolic acid B on high glucose-induced phenotypic transition and extracellular matrix secretion in human glomerular mesangial cells / 中国病理生理杂志

AIM:To investigate the effect of salvianolic acid B (Sal B) on high glucose-induced phenotypic transition and extracellular matrix (ECM) secretion in human glomerular mesangial cells (HGMCs) and the underlying mechanisms.METHODS:HGMCs were randomly divided into control group, high glucose group and high glucose plus high dose, medium dose and low dose of Sal B groups.The HGMCs except those in control group were exposed to high glucose (33.3 mmol/L) for 72 h, while those in Sal B groups were co-incubated with indicated concentrations of Sal B.The protein levels ofα-smooth muscle actin (α-SMA) , transforming growth () and phosphorylated Smad2 and p38 mitogen-activated protein kinase (MAPK) were determined by Western blot.The secretion levels of collagen type I (Col I) , collagen type III (Col III) , fibronectin (FN) and laminin (LN) were measured by ELISA.RESULTS:Exposure to high glucose markedly increased the protein expression ofI, Col III, FN and LN in the HG-MCs (P<0.01).The phosphorylation levels of Smad2 and p38 MAPK were also significantly increased (P<0.01).Coincubation with Sal B evidently decreased the protein expression ofI, Col III, FN and LN in the HGMCs induced by high glucose (P<0.05 or P<0.01).The phosphorylated levels of Smad2 and p38 MAPK were also reduced noticeably (P<0.05 or P<0.01).CONCLUSION:Sal B significantly suppresses high glucose-induced phenotypic transition and ECM secretion in the HGMCs, which might be attributed, at least partly, to inhibition ofSmad signaling pathway and p38 MAPK activation.

Effect of sesamin on pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary hypertension / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH).</p><p><b>METHOD</b>Totally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot.</p><p><b>RESULT</b>After the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC.</p><p><b>CONCLUSION</b>Sesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury.</p>

Effects of crocetin on VCAM-1 expression in human umbilical vein endothelial cells and monocyte-endothelial cell adhesion / 药学学报

Crocetin, a naturally occurring carotenoid, possesses antioxidant and antiatherosclerotic properties, of which the underlying mechanism remains unclear. In the present study, we examined the effects of crocetin (0.1, 1, 10 μmol·L(-1)) on angiotensin II (Ang II, 0.1 μmol·L(-1)) induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and monocyte-endothelial cell adhesion. The effects of crocetin on the activation of nuclear factor kappa B (NF-κB) and intracellular reactive oxygen species (ROS) were also observed. The results demonstrated that crocetin notably suppressed Ang II induced NF-κB activation (P<0.01) and VCAM-1 expression (P<0.05, P<0.01) in HUVECs, accompanied by a markedly reduced monocyte-endothelial cell adhesion (P<0.05, P<0.01). In addition, preincubation with crocetin resulted in a significant enhancement of cellular antioxidant capacity (P<0.05, P<0.01), while Ang II induced intracellular ROS decreased markedly (P<0.05, P<0.01). These results indicated that crocetin was capable of suppressing Ang II induced VCAM-1 expression and monocyte-endothelial cell adhesion by suppression of NF-κB activation, which might be derived from the enhancement of antioxidant capacity and subsequent reduction of intracellular ROS.

Effect of chrysin on expression of NOX4 and NF-κB in right ventricle of monocrotaline-induced pulmonary arterial hypertension of rats / 药学学报

The aim of the present study is to investigate the protective effect of chrysin (5,7-dihydroxyflavone) on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension (PAH). PAH rats were induced by a single injection of monocrotaline (60 mg x kg(-1), sc) and were administered with chrysin (50 or 100 mg x kg(-1) x d(-1)) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle (RV) to left ventricle (LV) + septum (S) and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expressions of collagen I, collagen III, NADPH oxidase 4 (NOX4) and nuclear factor-kappa B (NF-κB) were analyzed by immunohistochemisty, qPCR and (or) Western blot. The results showed that chrysin treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by chrysin. The expressions of NOX4, NF-κB and MDA contents were obviously decreased, while the T-AOC was significantly increased in right ventricule from PAH rats with chrysin treatment. These results suggest that chrysin ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of NOX4 expression and antioxidant activity, and inhibiting NF-κB expression and collagen accumulation.

Effects of rutaecarpine on right ventriclar remodeling in rats with monocrotaline-induced pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of rutaecarpine (Rut) on right ventricular remodeling in rats with monocrotaline-induced pulmonary hypertension (PH).</p><p><b>METHOD</b>Forty-eight SD rats were fed adaptively for 1 week and then were randomly divided into the following 4 groups (n = 12): normal control group, monocrotaline (MCT) treatment group, MCT treatment with Rut (20 mg/kg)group and MCT treatment with Rut (40 mg/kg) group. PH rats were induced by a single injection of monocrotaline (60 mg/kg, sc) and were administered with Rut (20 or 40 mg/kg/d) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. The ratio of right ventricle (RV) to left ventricle (LV) + septum (S) and the ratio of RV to tibial length were calculated. Right ventricular morphological changes were deserved by HE staining. Masson's trichrome staining was used to display collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. mRNA and protein expression levels of NOX4, collagen I and collagen III were analyzed by immunohistochemisty, real-time PCR and Western blot.</p><p><b>RESULTS</b>The results showed that Rut treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV + S and RV/Tibial length) of PH rats induced by monocrotaline. Furthermore, the right ventricular collagen deposition and collagen I and collagen I expression induced by MCT were both significantly suppressed by Rut. The expression levels of NOX4 and MDA were obviously decreased, while the T-AOC was significantly increased in right ventricular from PH rats treated with Rut.</p><p><b>CONCLUSION</b>These results suggested that Rut ameliorates the right ventricular remodeling in rats with PH induced by MCT through down-regulating of NOX4 expression and collagen accumulation.</p>

Effect of sequoyitol on expression of NOX4 and eNOS induced with glucose in human umbilical vein endothelial cells / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effect and mechanism of sequoyitol (Sep) on high glucose-induced human umbilical vein endothelial cells (HUVECs) injury.</p><p><b>METHODS</b>HUVECs were cultured with high glucose (30 mmol/L) in the presence or absence of sequoyitol (0.1, 1 and 10 micromol/L) for 24 h. Cell proliferation was measured by BrdU marking and cell cycle was detected by flow cytometry. 2', 7'-dichlorofluorescein diacetate was used to evaluate intracellular reactive oxygen species (ROS) levels. The NO, malonydialdehyde (MDA) and H2O2 levels were determined by colorimetric method according to the manufacturer's instructions. The expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase 4 (NOX4) were measured by real-time PCR and Western blot.</p><p><b>RESULTS</b>In the present study, we found that sequoyitol pretreatment for 1 h significantly decreased cell injury, promoted cell proliferation. Meanwhile sequoyitol significantly down-regulated NOX4 expression and decreased the level of ROS, MDA and H2O2 and obviously increased NO levels and up-regulated eNOS expression.</p><p><b>CONCLUSION</b>Sequoyitol alleviates high glucose-induced cell injuries in HUVECs via inhibiting oxidative stress and up-regulating eNOS expression.</p>

Effect of sequoyitol on expression of NOX4 and eNOS in aortas of type 2 diabetic rats / 药学学报

The aim of the present study is to investigate the effects of sequoyitol (Seq) on expression of eNOS and NOX4 in aortas of type 2 diabetic rats. Type 2 diabetic rats induced by high fat and high sugar diet and low dose of streptozotocin (STZ, 35 mg x kg(-1)) and were administered Seq (12.5, 25 and 50 mg x kg(-1) x d(-1)) for 6 weeks. The fasting blood glucose (FBG) and body weight were tested. Acetylcholine (Ach) induced endothelium-dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Aortic morphological change was observed with HE staining. The level of serum insulin was measured by radioimmunoassay. The total antioxidative capacity (T-AOC), malondialdehyde (MDA) and NO levels in aortas were determined according to the manufacturer's instructions. In addition, the expressions of eNOS and NOX4 in aortas were measured by immunohistochemisty, real-time PCR or Western blotting. The results showed that Seq significantly decreased FBG and insulin resistance, and improved aortic endothelium-dependent vasorelaxation function. The expressions of NOX4 and MDA content were obviously decreased, while the expression of eNOS, the levels of NO and T-AOC increased significantly in aortas of diabetic rats with Seq treatment. In conclusion, Seq protects against aortic endothelial dysfunction of type 2 diabetic rats through down-regulating expression of NOX4 and up-regulating eNOS expression.

Effects of sequoyitol on expression of NADPH oxidase subunits p22 phox and p47 phox in rats with type 2 diabetic liver disease / 药学学报

This study is to observe the effects of sequoyitol on the expression of NADPH oxidase subunits p22 phox and p47 phox in rats with type 2 diabetic liver diseases. The model of high fat and high sugar diet as well as intraperitoneal injection of small dose of streptozotocin (STZ, 35 mg x kg(-1)) induced diabetic rat liver disease was used. After sequoyitol (50, 25 and 12.5 mg x kg(-1)) was administrated for 6 weeks, the contents of blood glucose (BG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), NO and insulin (Ins) were measured, liver p22 phox and p47 phox mRNA content was determined with real-time PCR and the expression of p22 phox and p47 phox protein was examined by Western blotting. In addition, pathological changes in liver were observed with HE staining. Sequoyitol could reduce the content of fasting blood glucose, ALT, AST, Ins and H2O2, restore insulin sensitive index (ISI) and weight, elevate liver tissue T-AOC and NO content, reduce the NADPH oxidase subunit liver tissue p22 phox and p47 phox mRNA and protein expression, as well as ameliorate liver pathologic lesions. The results showed that sequoyitol can ease the type 2 diabetic rat liver oxidative stress by lowering NADPH oxidase expression.

Anti-lipotoxic action of sesamin on renovascular hypertensive rats fed with a high-fat, high-sucrose diet / 药学学报

This study is to observe anti-lipotoxic effect of sesamin on renovascular hypertensive rats fed with a high-fat, high-sucrose diet. Thirty-four complex model rats were induced by two-kidney, one-clip method and on high-fat and refined-carbohydrate diet for thirteen weeks. From the fifth week, intragastric administration of sesamin (120, 60 and 30 mg x kg(-1) x d(-1)) lasted for eight weeks. Blood pressure (BP), blood fat (BF), blood glucose (BG), free fatty acids (FFA), insulin (Ins), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were determined. Pathological changes of pancreas, perirenal fat and liver were semiquantitatively analyzed. In sesamin (120 and 60 mg x kg(-1) x d(-1)) group, it was found that there were decrease of levels of BP, BF, BG, TNF-alpha, IL-6 and FFA, improvement of insulin resistance and glucose tolerance, alleviation of body weight, humid weight of fat, liver and pancreas and their organ index, and reduction of islet cell hyperplasia and amount of lipid droplet vacuoles in lipocyte and hepatocyte. It is implied that sesamin had anti-lipotoxic effect and its mechanism may be closely associated with the amelioration of insulin resistance via reducing lipidoses in hepatocyte and inflammatory adipokines such as TNF-alpha and IL-6.