Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was ...undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling.
An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H2O2-induced oxidative stress in EA.hy926 endothelial cells.
Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-β, β-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner.
Taken together, these results suggest that SA may have beneficial role in the treatment of hypertensive heart disease by attenuating fibrosis and oxidative stress through its antioxidant potential.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Synthesis of copper oxide nanoparticles without any chemical reductant is always a challenging methodology for biological studies. In this study, sinapic acid, a phytochemical, is used for the ...synthesis of stable copper oxide nanoparticles. The as-synthesized nanoparticles were characterized thoroughly using UV–Visible, IR spectroscopy, Transmission Electron Microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Nanoparticles collected during different time intervals of synthesis (60,120 and 180 min) were subjected for analysis, where the occurrence of copper oxide nanoparticles with substantial morphology was seen at 180 min. Further, nanoparticles synthesized at 120 and 180 min were studied for their potential biological applications. These copper oxide nanoparticles evinced potential cytotoxic effects on breast cancer cells, MCF7 and MDA-MB231. Supplementarily, it also exhibited anti-angiogenic effect on endothelial cells (EA.hy926), thus confirming its potential to inhibit angiogenesis in cancer.
Graphic abstract
•Sinapic acid improves cardiac functional recovery in reperfused heart.•Sinapic acid attenuates LDH activity and myocardial injury in reperfused heart.•Sinapic acid prevents lipid peroxidation and ...mitochondrial dysfunction.•Sinapic acid protects H9c2 cardiomyoblast cells against oxidative stress.
The present study was designed to evaluate antioxidant and cardioprotective potential of sinapic acid (SA) against ischemia/reperfusion (I/R) injury. Cardiac functional recovery after I/R was evaluated by percentage rate pressure product (%RPP) and percentage coronary flow (%CF). Myocardial injury was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining and LDH enzyme leakage. Oxidative stress was estimated by lipid peroxidation level. eNOS protein expression in reperfused heart was assessed using Western blot method. Finally, in order to support the antioxidant effect of SA, in vitro protective potential of SA was assessed on H2O2-induced oxidative stress in H9c2 cardiomyoblast cells. The overall results demonstrated that I/R induced cardiac dysfunction, injury and oxidative stress was attenuated by SA treatment. Moreover, in vitro results also shown that, SA protects H9c2 cells from oxidative stress and modulates mitochondrial membrane permeability transition (MPT). In conclusion, coupled results from both in vivo and in vitro experiments have confirmed that SA with antioxidant role protects cardiac cells and its functions from I/R induced oxidative stress.
Objective: To investigate the effects of Gymnema montanum leaf extract against endoplasmic reticulum (ER) stress-induced toxicity in endothelial cells.Methods: The immortalized endothelial hybrid ...cell, EA.hy926 was treated with different concentrations of Gymnema montanum leaf extract (0-100 μg/mL) and the ER stress inducer, tunicamycin. The cytotoxicity was assessed by MTT as well as lactate dehydrogenase and malondialdehyde levels were determined. The levels of ER stress markers, GRP78 and CHOP were analysed by Western blot assay. The Gymnema montanum leaf extract-mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) was assessed by cell-based luciferase enzyme fragment complementation assay and antioxidant responsive element driven luciferase reporter assay. The levels of phosphoproteins of the MAPK pathway were analyzed using the Bioplex system. Results: A dose-dependent cytoprotective effect of Gymnema montanum leaf extract was observed in tunicamycin-induced toxicity. Gymnema montanum leaf extract significantly reduced lactate dehydrogenase activity and malondialdehyde levels in ER stress-induced endothelial cells. It also suppressed ER stress markers dose dependently and inhibited the phosphorylation of JNK, ERK, MEK and p38 MAPK in tunicamycin-induced endothelial cells. Moreover, Gymnema montanum leaf extract increased the expression of Nrf2 and its downstream targets in endothelial cells. Conclusions: Gymnema montanum leaf extract attenuates ER stress by increasing the expression of Nrf2 and its downstream genes.
This article evaluates the effect of wear parameters on composite materials. Aluminium alloy 7178 alloys with various nano titanium diboride weight percentages were prepared using stir casting. A ...pin-and-disc test rig was utilized to carry out the dry sliding wear test. Using Taguchi’s experiments for optimization, the L27 orthogonal array was designed (D.O.E.). The SNR and ANOVA techniques were used to identify the percentage of responses attributable to the input parameters. Both the wear rate and coefficient of friction increased with higher loading levels. This parameter, load intensity, had the most significant influence on wear rate and C.O.F. and sliding distance and velocity. Material removal was prevented at all times by nano titanium diboride particles embedded in the matrix alloy. AA7178 was treated with nano titanium diboride particles to improve its wear resistance.
Endoplasmic reticulum (ER) stress attributes a crucial role in diabetes-induced endothelial dysfunction. The present study investigated the effects of quercetin, a potent antioxidant on the ...attenuation of ER stress-modulated endothelial dysfunction in streptozotocin (STZ)-induced diabetic rats. Oral administration of quercetin for six weeks to diabetic rats dose-dependently reduced the blood glucose levels and improved insulin secretion. Histopathological examination of pancreatic tissues in diabetic rats showed pathological changes such as shrunken islets, reduction in islet area and distorted β-cells, which were found to be restored by quercetin treatment. In addition, quercetin reduced the pancreatic ER stress-induced endothelial dysfunction as assessed by immunohistochemical analysis of C/ERB homologous protein (CHOP) and endothelin-1 (ET-1). Moreover, quercetin administration progressively increased the expression of vascular endothelial growth factor (VEGF) and its receptor, VEGFR2 in diabetes rats. Quercetin-mediated decrease in the nitric oxide (NO∙) and cyclic 3′,5′- guanosine monophosphate (cGMP) levels were also observed in the diabetic rats. Quercetin treatment reduced the lipid peroxidation in the diabetic rats, meanwhile increased the total antioxidant capacity in the pancreas from diabetic rats. Altogether, these results demonstrated the vasoprotective effect of quercetin against STZ-induced ER stress in the pancreas of diabetic rats.
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<正>Objective:To determine the phenolic content in Codariocalyx motorius root extract and to evaluate its antioxidant properties using various in vitro assay systems.Methods:The antioxidant ...activity was evaluated based on scavenging of 1,1—diphenyl—2—picrylhydrazyl,hydroxyl radicals,superoxide anions,nitric oxide,hydrogen peroxide,peroxvnilrile,reducing power and by inhibition oi lipid peroxidation which was estimated in terms of thiohurhituric acid reactive substances.Results:The root extract of the Codariocalyx motorius(C.motorius) exhibited potent total antioxidant activity that increased with increasing amount of extract concentration,which was compared with standard drug such as quercetin.butylaled hvdroxvloluene.tocopherol at different concentrations.The different concentrations of the extracts showed inhibition on lipid peroxidation.In addition,the extracts had effective reducing power,free radical scavenging, super oxide anion scavenging,nitric oxide scavenging,lipid peroxidation,and total phenolic content depending on concentration.High correlation between total phenolic contents and scavenging potential of different reactive oxygen species(r~2=0.83 1 -0.978) indicated the polyphenols as the main antioxidants.Conclusions:Codariocalyx motorius(C.motorius) root possess the highly active antioxidant substance which can be used for the treatment of oxidative stress-related diseases.
Dietary compounds like flavonoids may offer protection against neurodegeneration. Huntington’s disease (HD) is a neurodegenerative disorder characterized by symptoms like chorea and dementia. ...3-Nitropropionic acid (3-NP), a Succinate dehydrogenase (SDH) inhibitor produces behavioral, biochemical and histological changes in the striatum, mimics HD in animals and humans. The present study was designed to examine the protective activity of Rutin (RT), a primary flavonoid from citrus fruits, green tea on 3-NP induced experimental model of HD in rats. Rats were pretreated with Rutin, a potent antioxidant (25 and 50 mg/kg b.w.) orally prior to the intraperitoneally (i.p.) administration of 3-NP (10 mg/kg b.w.) for 14 days. Behavioral assessments were carried out on 5th, 10th and 15th day after 3-NP treatment. Body weight, biochemical and histological studies were analyzed on 15th day. Systemic administration of 3-NP significantly reduced the body weight, locomotor activities (Rota rod, Open field test), memory (Morris water maze) and antioxidants such as Glutathione (GSH) levels, activities of Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione-S-transferase (GST), Glutathione reductase (GR). 3-NP also produces striatal damage by increased the levels of lipid peroxides, nitrite, Glial Fibrillary Acidic Protein (GFAP) and activity of Acetylcholine esterase (AchE). Thus, Rutin treatment of 25 and 50 mg/kg b.w. has significantly restored all the biochemical, behavioral and histological alterations caused by the 3-NP through its antioxidant activity. The findings of our study indicates that Rutin may have an important role in protecting the striatum from oxidative/nitrosative insults caused by 3-NP. These results suggest that RT might be a drug of choice to treat HD.
Abstract
The concrete industry introduces a variety of linked ways for integrating and using waste materials that are generally usable, readily accessible, and financially feasible for the everyday ...consumer. The use of such components in cementitious materials not just to saves greenhouse gas emissions, but also improves flowability and longevity significantly. This article discusses how rice husk ash (RHA), a byproduct of rice production, may be used with cementitious material. Because the density of concrete incorporating RHA is comparable to that of standard weight cement, it may also be used for a wide variety of applications. RHA concrete's impermeable substructure provides superior resistance against chemical attack, salt entry, and bubbling, among other things. RHA cementitious material has excellent contraction characteristics and increases the durability of the concretes. In this work, the RHA was used in progressive fractions such as, 0%, 10%, 20%, 30%, and 40% as a substitute for the fine sand in different periods. The outcomes evidenced that the incorporation of 20% replacement of RHA with fine sand showed a better increment in the compressive strength of the concrete.
Endothelial cell activation through nuclear factor-kappa-B (NFkB) and mitogen-activated protein kinases leads to increased biosynthesis of pro-inflammatory mediators, cellular injury and vascular ...inflammation under lipopolysaccharide (LPS) exposure. Recent studies report that LPS up-regulated global methyltransferase activity. In this study, we observed that a combination treatment with metformin (MET) and cholecalciferol (VD) blocked the LPS-induced S-adenosylmethionine (SAM)-dependent methyltransferase (SDM) activity in Eahy926 cells. We found that LPS challenge (i) increased arginine methylation through up-regulated protein arginine methyltransferase-1 (PRMT1) mRNA, intracellular concentrations of asymmetric dimethylarginine (ADMA) and homocysteine (HCY); (ii) up-regulated cell senescence through mitigated sirtuin-1 (SIRT1) mRNA, nicotinamide adenine dinucleotide (NAD+) concentration, telomerase activity and total antioxidant capacity; and (iii) lead to endothelial dysfunction through compromised nitric oxide (NOx) production. However, these LPS-mediated cellular events in Eahy926 cells were restored by the synergistic effect of MET and VD. Taken together, this study identified that the dual compound effect inhibits LPS-induced protein arginine methylation, endothelial senescence and dysfunction through the components of epigenetic machinery, SIRT1 and PRMT1, which is a previously unidentified function of the test compounds. In silico results identified the presence of vitamin D response element (VDRE) sequence on PRMT1 suggesting that VDR could regulate PRMT1 gene expression. Further characterization of the cellular events associated with the dual compound challenge, using gene silencing approach or adenoviral constructs for SIRT1 and/or PRMT1 under inflammatory stress, could identify therapeutic strategies to address the endothelial consequences in vascular inflammation-mediated atherosclerosis.
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•MET+VD reduced the LPS-induced SDM activity and protein arginine methylation by restoring the normal PRMT1 mRNA, ADMA & HCY.•MET+VD improved several senescence indicators such as endothelial cell cycle arrest, SIRT1 mRNA, telomerase activity and NAD+.•Identification of in silico VDRE sequence on PRMT1 suggests that vitamin D receptor could regulate PRMT1 transcription.•SIRT1 and PRMT1 can be potential targets for the combined effect in reducing the LPS-induced endothelial stress responses.
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