Sinapic acid prevents hypertension and cardiovascular remodeling in pharmacological model of nitric oxide inhibited rats.

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

Sinapic acid prevents deregulated expression of cardiovascular genes.

<p>(A) Relative expression fold changes of TGF-β and β-MHC mRNAs in heart. (B) Relative expression negative fold change of eNOS mRNA in aorta. (C) Differential eNOS protein expression in aorta and its normalized value with β-actin. Values are expressed as means ± SD. All experiments were done in triplicates. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs L-NAME.</p

Sinapic acid improved cardiovascular function in experimental hypertensive rats.

<p>(A) Evaluation of ventricular function in heart of various experimental groups. (B) Cumulative concentration-response curves of Ach induced relaxation in endothelium-intact aortic rings. (C) Cumulative concentration-response curves of SNP induced relaxation in endothelium-intact aortic rings. Values are expressed as mean ± SD. n = 6 per group. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs L-NAME.</p

acid decreases total ROS and improves NO level in EA.hy926 cells.

<p>10 µM SA was pre-treated for 24 h prior to incubation of cells with 300 µM of H₂O₂ for 4 h. (A) Intracellular total ROS level was measured by the fluorescent probe DCFH-DA and the images were obtained by fluorescence microscopy. (B) NO level was measured by the fluorescent probe DAR-4M AM and the images were obtained by fluorescence microscopy. The representative images from three independent experiments are shown. (C) Total ROS fluorescence intensity value was calculated using Adobe Photoshop version 7.0. (D) Fluorescence intensity measurement against NO was calculated using Adobe Photoshop version 7.0. RFU: Relative Fluorescence Unit. Values are expressed as mean ± SEM. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs H₂O₂.</p

Sinapic acid restores nitric oxide metabolites level and ACE activity in experimental hypertensive rats.

<p>(A) Estimation of nitric oxide metabolites level in various experimental groups. (B) Assessment of ACE activity in various experimental groups. Values are expressed as mean ± SD. n = 6 per group. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs L-NAME.</p

Sinapic acid prevented oxidative stress.

<p>U^*  =  enzyme concentration required to inhibit the chromogen produced by 50% in one minute under standard condition. U^#  =  μM of H₂O₂ consumed/minute. U^$  =  μg of GSH utilized/minute. Values are expressed as mean ± SD.</p><p>^*<i>P</i><0.05 vs control;</p>#<p><i>P</i><0.05 vs L-NAME; n  =  6 per group.</p><p>Sinapic acid prevented oxidative stress.</p

Transcriptomic Analysis of Thalidomide Challenged Chick Embryo Suggests Possible Link between Impaired Vasculogenesis and Defective Organogenesis

Since the conception of thalidomide as a teratogen, approximately 30 hypotheses have been put forward to explain the developmental toxicity of the molecule. However, no systems biology approach has been taken to understand the phenomena yet. The proposed work was aimed to explore the mechanism of thalidomide toxicity in developing chick embryo in the context of transcriptomics by using genome wide RNA sequencing data. In this study, we challenged the developing embryo at the stage of blood island formations (HH8), which is the most vulnerable stage for thalidomide-induced deformities. We observed that thalidomide affected the early vasculogenesis through interfering with the blood island formation extending the effect to organogenesis. The transcriptome analyses of the embryos collected on sixth day of incubation showed that liver, eye, and blood tissue associated genes were down regulated due to thalidomide treatment. The conserved gene coexpression module also indicated that the genes involved in lens development were heavily affected. Further, the Gene Ontology analysis explored that the pathways of eye development, retinol metabolism, and cartilage development were dampened, consistent with the observed deformities of various organs. The study concludes that thalidomide exerts its toxic teratogenic effects through interfering with early extra-embryonic vasculogenesis and ultimately gives an erroneous transcriptomic pattern to organogenesis