The Experts below are selected from a list of 22932 Experts worldwide ranked by ideXlab platform
Suvro Chatterjee - One of the best experts on this subject based on the ideXlab platform.
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prevention of cardiac dysfunction Kidney Fibrosis and lipid metabolic alterations in l name hypertensive rats by sinapic acid role of hmg coa reductase
European Journal of Pharmacology, 2016Co-Authors: Thangarasu Silambarasan, Jeganathan Manivannan, Boobalan Raja, Suvro ChatterjeeAbstract:Abstract The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, Kidney Fibrosis and lipid alterations in Nω-nitro- l -arginine methyl ester hydrochloride ( l -NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and Kidney), lipid peroxidation products in tissues (liver and Kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l -NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l -NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l -NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of −5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, Kidney Fibrosis and lipid alterations.
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prevention of cardiac dysfunction Kidney Fibrosis and lipid metabolic alterations in l name hypertensive rats by sinapic acid role of hmg coa reductase
European Journal of Pharmacology, 2016Co-Authors: Thangarasu Silambarasan, Jeganathan Manivannan, Boobalan Raja, Suvro ChatterjeeAbstract:Abstract The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, Kidney Fibrosis and lipid alterations in Nω-nitro- l -arginine methyl ester hydrochloride ( l -NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and Kidney), lipid peroxidation products in tissues (liver and Kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l -NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l -NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l -NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of −5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, Kidney Fibrosis and lipid alterations.
Jeganathan Manivannan - One of the best experts on this subject based on the ideXlab platform.
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prevention of cardiac dysfunction Kidney Fibrosis and lipid metabolic alterations in l name hypertensive rats by sinapic acid role of hmg coa reductase
European Journal of Pharmacology, 2016Co-Authors: Thangarasu Silambarasan, Jeganathan Manivannan, Boobalan Raja, Suvro ChatterjeeAbstract:Abstract The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, Kidney Fibrosis and lipid alterations in Nω-nitro- l -arginine methyl ester hydrochloride ( l -NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and Kidney), lipid peroxidation products in tissues (liver and Kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l -NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l -NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l -NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of −5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, Kidney Fibrosis and lipid alterations.
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prevention of cardiac dysfunction Kidney Fibrosis and lipid metabolic alterations in l name hypertensive rats by sinapic acid role of hmg coa reductase
European Journal of Pharmacology, 2016Co-Authors: Thangarasu Silambarasan, Jeganathan Manivannan, Boobalan Raja, Suvro ChatterjeeAbstract:Abstract The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, Kidney Fibrosis and lipid alterations in Nω-nitro- l -arginine methyl ester hydrochloride ( l -NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and Kidney), lipid peroxidation products in tissues (liver and Kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l -NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l -NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l -NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of −5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, Kidney Fibrosis and lipid alterations.
Raghu Kalluri - One of the best experts on this subject based on the ideXlab platform.
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partial epithelial to mesenchymal transition and other new mechanisms of Kidney Fibrosis
Trends in Endocrinology and Metabolism, 2016Co-Authors: Sara Lovisa, Raghu Kalluri, Michael ZeisbergAbstract:Kidney Fibrosis is the unavoidable consequence of chronic Kidney disease irrespective of the primary underlying insult. It is a complex phenomenon governed by the interplay between different cellular components and intricate networks of signaling pathways, which together lead to loss of renal functionality and replacement of Kidney parenchyma with scar tissue. An immense effort has recently been made to understand the molecular and cellular mechanisms leading to Kidney Fibrosis. The cellular protagonists of this process include myofibroblasts, tubular epithelial cells, endothelial cells, and immune cells. We discuss here the most recent findings, including partial epithelial-to-mesenchymal transition (EMT), in the initiation and progression of tissue Fibrosis and chronic Kidney disease (CKD). A deep understanding of these mechanisms will allow the development of effective therapies.
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tet3 mediated hydroxymethylation of epigenetically silenced genes contributes to bone morphogenic protein 7 induced reversal of Kidney Fibrosis
Journal of The American Society of Nephrology, 2014Co-Authors: Bjorn Tampe, Elisabeth M Zeisberg, Gerhard A Muller, Claudia A Muller, Raghu Kalluri, Valerie S. Lebleu, Hikaru Sugimoto, Desiree Tampe, Michael ZeisbergAbstract:Methylation of CpG island promoters is an epigenetic event that can effectively silence transcription over multiple cell generations. Hypermethylation of the Rasal1 promoter contributes to activation of fibroblasts and progression of Kidney Fibrosis. Here, we explored whether such causative hypermethylation could be reversed through endogenous mechanisms and whether such reversal of hypermethylation is a constituent of the antifibrotic activity of bone morphogenic protein 7 (BMP7). We show that successful inhibition of experimental Kidney Fibrosis through administration of BMP7 associates with normalization of Rasal1 promoter hypermethylation. Furthermore, this reversal of pathologic hypermethylation was achieved specifically through Tet3-mediated hydroxymethylation. Collectively, our findings reveal a new mechanism that may be exploited to facilitate therapeutic DNA demethylation to reverse Kidney Fibrosis.
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origin and function of myofibroblasts in Kidney Fibrosis
Nature Medicine, 2013Co-Authors: Valerie S. Lebleu, Gangadhar Taduri, Yingqi Teng, Vesselina G. Cooke, Craig B. Woda, Hikaru Sugimoto, Joyce T Oconnell, Raghu KalluriAbstract:Myofibroblasts are associated with organ Fibrosis, but their origin and functional role remain unknown. Using multiple genetically engineered mice, the authors found that in the Kidney, myofibroblasts arise from multiple sources—resident fibroblasts, bone marrow, endothelial cells and epithelial cells. Targeting these different populations may therefore be required to inhibit the accumulation of myofibroblasts in Kidney Fibrosis.
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Origin and function of myofibroblasts in Kidney Fibrosis.
Nature medicine, 2013Co-Authors: Valerie S. Lebleu, Gangadhar Taduri, Joyce T. O’connell, Yingqi Teng, Vesselina G. Cooke, Craig B. Woda, Hikaru Sugimoto, Raghu KalluriAbstract:Myofibroblasts are associated with organ Fibrosis, but their precise origin and functional role remain unknown. We used multiple genetically engineered mice to track, fate map and ablate cells to determine the source and function of myofibroblasts in Kidney Fibrosis. Through this comprehensive analysis, we identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts through proliferation. The nonproliferating myofibroblasts derive through differentiation from bone marrow (35%), the endothelial-to-mesenchymal transition program (10%) and the epithelial-to-mesenchymal transition program (5%). Specific deletion of Tgfbr2 in α-smooth muscle actin (αSMA)(+) cells revealed the importance of this pathway in the recruitment of myofibroblasts through differentiation. Using genetic mouse models and a fate-mapping strategy, we determined that vascular pericytes probably do not contribute to the emergence of myofibroblasts or Fibrosis. Our data suggest that targeting diverse pathways is required to substantially inhibit the composite accumulation of myofibroblasts in Kidney Fibrosis.
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identification of human epididymis protein 4 as a fibroblast derived mediator of Fibrosis
Nature Medicine, 2013Co-Authors: Valerie S. Lebleu, Gerhard A Muller, Yingqi Teng, Hikaru Sugimoto, Joyce T Oconnell, David M Charytan, C A Muller, Raghu KalluriAbstract:The functional contribution of myofibroblasts in Fibrosis is not well understood. Using a new genetic mouse model to track and isolate myofibroblasts, we performed gene expression profiling followed by biological validation to identify HE4 (encoding human epididymis protein 4, also known as WAP 4-disulfide core domain-2 or Wfdc2) as the most upregulated gene in Fibrosis-associated myofibroblasts. The HE4 gene encodes for a putative serine protease inhibitor that is upregulated in human and mouse fibrotic Kidneys and is elevated in the serum of patients with Kidney Fibrosis. HE4 suppresses the activity of multiple proteases, including serine proteases and matrix metalloproteinases, and specifically inhibits their capacity to degrade type I collagen. In particular, we identified two serine proteases, Prss35 and Prss23, as HE4 targets with functional relevance in Kidney Fibrosis. Administration of HE4-neutralizing antibodies accelerated collagen I degradation and inhibited Fibrosis in three different mouse models of renal disease. Collectively these studies suggest that HE4 is a potential biomarker of renal Fibrosis and a new therapeutic target.
Youhua Liu - One of the best experts on this subject based on the ideXlab platform.
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tubule derived wnts are required for fibroblast activation and Kidney Fibrosis
Journal of The American Society of Nephrology, 2017Co-Authors: Dong Zhou, Lu Zhang, Ke Zhang, Yali Min, Liangxiang Xiao, Lin Lin, Sheldon Bastacky, Youhua LiuAbstract:Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal Fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β-catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal Fibrosis after obstructive or ischemia-reperfusion injury. In vitro, incubation of normal rat Kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with Kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and Kidney Fibrosis via epithelial-mesenchymal communication.
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matrix metalloproteinase 7 is a urinary biomarker and pathogenic mediator of Kidney Fibrosis
Journal of The American Society of Nephrology, 2017Co-Authors: Dong Zhou, Lili Zhou, Yuan Tian, Roderick J Tan, Liangxiang Xiao, Fan Fan Hou, Ling Sun, Jianwei Tian, Youhua LiuAbstract:Matrix metalloproteinase-7 (MMP-7), a secreted zinc- and calcium-dependent endopeptidase, is a transcriptional target of canonical Wnt/β-catenin signaling. Because Wnt/β-catenin is activated in diseased Kidney, we hypothesized that urinary MMP-7 level may be used as a noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, we conducted a cross-sectional study, measuring urinary MMP-7 levels in a cohort of 102 patients with CKD. Compared with normal subjects, patients with various Kidney disorders had markedly elevated urinary levels of MMP-7. Furthermore, urinary MMP-7 levels closely correlated with renal Fibrosis scores in patients. In mice, knockout of MMP-7 ameliorated the fibrotic lesions and expression of matrix genes induced by obstructive injury. Genetic ablation of MMP-7 also preserved E-cadherin protein expression and substantially reduced the expression of total and dephosphorylated β-catenin and the de novo expression of vimentin and fibroblast-specific protein 1 in renal tubules of obstructed Kidneys. In vitro, MMP-7 proteolytically degraded E-cadherin in proximal tubular cells, leading to β-catenin liberation and nuclear translocation and induction of β-catenin target genes by a mechanism independent of Wnt ligands. Finally, pharmacologic inhibition of MMP-7 immediately after obstructive injury reduced renal Fibrosis in vivo These results suggest that MMP-7 not only can serve as a noninvasive biomarker but also is an important pathogenic mediator of Kidney Fibrosis.
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renal Fibrosis in 2015 understanding the mechanisms of Kidney Fibrosis
Nature Reviews Nephrology, 2016Co-Authors: Dong Zhou, Youhua LiuAbstract:The year 2015 has seen great progress in the renal Fibrosis field, as key studies began to build a consensus on the importance of epithelial-to-mesenchymal transition, cell cycle arrest, and defective metabolism in the pathogenesis of Kidney Fibrosis. New findings also point to a role of developmental signalling in renal fibrogenesis.
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wnt β catenin signaling and Kidney Fibrosis
Kidney International, 2014Co-Authors: Roderick J Tan, Dong Zhou, Lili Zhou, Youhua LiuAbstract:Wnt/β-catenin signaling is an evolutionarily conserved, highly complex, key developmental pathway that regulates cell fate, organ development, tissue homeostasis, as well as injury and repair. Although relatively silent in normal adult Kidney, Wnt/β-catenin signaling is re-activated after renal injury in a wide variety of animal models and in human Kidney disorders. Whereas some data point to a protective role of this signaling in healing and repair after acute Kidney injury, increasing evidence suggests that sustained activation of Wnt/β-catenin is associated with the development and progression of renal fibrotic lesions. In Kidney cells, Wnt/β-catenin promotes the expression of numerous Fibrosis-related genes such as Snail1, plasminogen activator inhibitor-1, and matrix metalloproteinase-7. Recent studies also indicate that multiple components of the renin–angiotensin system are the direct downstream targets of Wnt/β-catenin. Consistently, inhibition of Wnt/β-catenin signaling by an assortment of strategies ameliorates Kidney injury and mitigates renal fibrotic lesions in various models of chronic Kidney disease, suggesting that targeting this signaling could be a plausible strategy for therapeutic intervention. In this mini review, we will briefly discuss the regulation, downstream targets, and mechanisms of Wnt/β-catenin signaling in the pathogenesis of Kidney Fibrosis.
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new insights into epithelial mesenchymal transition in Kidney Fibrosis
Journal of The American Society of Nephrology, 2010Co-Authors: Youhua LiuAbstract:Epithelial-mesenchymal transition (EMT), a process by which differentiated epithelial cells undergo a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury. However, the degree to which this process contributes to Kidney Fibrosis remains a matter of intense debate and is likely to be context-dependent. EMT is often preceded by and closely associated with chronic interstitial inflammation and could be an adaptive response of epithelial cells to a hostile or changing microenvironment. In addition to tubular epithelial cells, recent studies indicate that endothelial cells and glomerular podocytes may also undergo transition after injury. Phenotypic alteration of podocytes sets them in motion to functional impairment, resulting in proteinuria and glomerulosclerosis. Several intracellular signal transduction pathways such as TGFβ/Smad, integrin-linked kinase (ILK) and Wnt/β-catenin signaling are essential in controlling the process of EMT and presently are potential targets of antifibrotic therapy. This review highlights the current understanding of EMT and its underlying mechanisms to stimulate further discussion on its role, not only in the pathogenesis of renal interstitial Fibrosis but also in the onset of podocyte dysfunction, proteinuria, and glomerulosclerosis.
Thangarasu Silambarasan - One of the best experts on this subject based on the ideXlab platform.
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prevention of cardiac dysfunction Kidney Fibrosis and lipid metabolic alterations in l name hypertensive rats by sinapic acid role of hmg coa reductase
European Journal of Pharmacology, 2016Co-Authors: Thangarasu Silambarasan, Jeganathan Manivannan, Boobalan Raja, Suvro ChatterjeeAbstract:Abstract The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, Kidney Fibrosis and lipid alterations in Nω-nitro- l -arginine methyl ester hydrochloride ( l -NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and Kidney), lipid peroxidation products in tissues (liver and Kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l -NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l -NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l -NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of −5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, Kidney Fibrosis and lipid alterations.
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prevention of cardiac dysfunction Kidney Fibrosis and lipid metabolic alterations in l name hypertensive rats by sinapic acid role of hmg coa reductase
European Journal of Pharmacology, 2016Co-Authors: Thangarasu Silambarasan, Jeganathan Manivannan, Boobalan Raja, Suvro ChatterjeeAbstract:Abstract The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, Kidney Fibrosis and lipid alterations in Nω-nitro- l -arginine methyl ester hydrochloride ( l -NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and Kidney), lipid peroxidation products in tissues (liver and Kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l -NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l -NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l -NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of −5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, Kidney Fibrosis and lipid alterations.
