Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-κB

Chiu, Jane; Khan, Zia A.; Farhangkhoee, Hana; Chakrabarti, Subrata

doi:10.1016/j.nut.2008.12.007

Cited by 170 publications

(126 citation statements)

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“…The pharmacological safety of curcumin has previously been demonstrated in various animal models, and curcumin is nontoxic even at high doses (3). Previous studies have demonstrated that curcumin has antioxida, anti-inflammatory, anti-proliferative, pro-apoptotic and anti-carcinogenic properties (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Curcumin suppresses transforming growth factor-β1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways

Liu

Shi

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The differentiation of cardiac fibroblasts (CFs) into myofibroblasts and the subsequent deposition of the extracellular matrix is associated with myocardial fibrosis following various types of myocardial injury. In the present study, the effect of curcumin, which is a pharmacologically-safe natural compound from the Curcuma longa herb, on transforming growth factor (TGF)-β1-induced CFs was investigated, and the underlying molecular mechanisms were examined. The expression levels of α-smooth muscle actin (SMA) stress fibers were investigated using western blotting and immunofluorescence in cultured neonatal rat CFs. Protein and mRNA expression levels of α-SMA and collagen type I (ColI) were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. In addition, the activation of Smad2 and p38 was examined using western blotting. Curcumin, SB431542 (a TGF-βR-Smad2 inhibitor) and SB203580 (a p38 inhibitor) were used to inhibit the stimulation by TGF-β1. The results demonstrated that the TGF-β1-induced expression of α-SMA and ColI was suppressed by curcumin at the mRNA and protein levels, while SB431542 and SB203580 induced similar effects. Furthermore, phosphorylated Smad-2 and p38 were upregulated in TGF-β1-induced CFs, and these effects were substantially inhibited by curcumin administration. In conclusion, the results of the present study demonstrated that treatment with curcumin effectively suppresses TGF-β1-induced CF differentiation via Smad-2 and p38 signaling pathways. Thus, curcumin may be a potential therapeutic agent for the treatment of cardiac fibrosis. IntroductionCardiac fibroblast differentiation, excessive biosynthesis and destruction of the interstitial extracellular matrix (ECM) in the ventricles of the heart are key features of cardiac fibrosis, which is a consequence of cardiac remodeling initiated by pathological events associated with various cardiovascular disorders (1). Induced by transforming growth factor (TGF)-β1 and other factors, cardiac fibroblasts (CFs) differentiate into α-smooth muscle actin (SMA) fiber-rich cardiac myofibroblasts that facilitate contractility and increase ECM modulation ability (1). Although these changes are important for wound repair and are beneficial for the maintenance of cardiac function, continuous myocardial fibrosis may result in abnormal myocardial stiffness and, ultimately, ventricular dysfunction (1).Curcumin, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3,5-dione, is a natural polyphenolic compound from the Curcuma longa herb, possessing multiple biological and medicinal activities (2). The pharmacological safety of curcumin has previously been demonstrated in various animal models, and curcumin is nontoxic even at high doses (3). Previous studies have demonstrated that curcumin has antioxida, anti-inflammatory, anti-proliferative, pro-apoptotic and anti-carcinogenic properties (4-8). Furthermore, previous investigations into the effects of curcumin in heart disease have indicated that curcumin has...

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Section: Introductionmentioning

confidence: 99%

Curcumin suppresses transforming growth factor-β1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways

Liu

Shi

et al. 2016

Experimental and Therapeutic Medicine

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“…Hyperglycemia is the key initiating factor in the development of all chronic diabetic complications including diabetic nephropathy. It has been hypothesized that an increase in oxidative stress as a result of chronic hy- perglycemia activates several signaling pathways that alter gene expression (Chiu et al, 2009). Recent studies have suggested that inflammation plays a role in the progression of diabetic nephropathy (Fujita et al, 2008;Ko et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes

et al. 2011

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Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.

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“…Implication of oxidative stress in the pathogenesis of diabetes mellitus is suggested not only by oxygen free radical generation but also due to non-enzymatic protein glycosylation, auto-oxidation of glucose, impairment of antioxidant enzymes and the formation of peroxides (10) . Free radical-mediated lipid peroxidation (LPO) is a key factor in the development of diabetic liver complications (11) .…”

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confidence: 99%

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

George¹,

Kumar

Antony

et al. 2012

Br J Nutr

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Diabetes mellitus is a growing health problem worldwide and is associated with severe liver complications. The aim of the present study is to analyse the status of metabolic and free-radical-scavenging enzymes and second messengers in the liver of streptozotocin (STZ)-induced diabetic rats, and to determine the hepatoprotective role of vitamin D 3 . All studies were performed using the liver of adult male Wistar rats. Gene expression studies were carried out using real-time PCR with specific probes. Second messenger levels were determined using 3 H-labelled Biotrak assay kits, and glucose uptake assay with D-[ 14 C]glucose. The present results show that there was a decrease in hepatic glucose uptake, malate dehydrogenase activity, glycogen content, inositol triphosphate (IP 3 ) and cyclic GMP levels, and superoxide dismutase, glutathione peroxidase, phospholipase C, cyclic AMP-responsive element-binding protein, vitamin D receptor (VDR) and insulin receptor (INSR) gene expression in the diabetic rats when compared with the controls (all P,0·05), while cyclic AMP levels and GLUT2 expression were increased (P,0·05). Treatment of the diabetic rats with vitamin D 3 and insulin reversed the altered parameters to near control values. In conclusion, the data suggest a novel role of vitamin D 3 in restoring impaired liver metabolism in STZ-induced diabetic rats by regulating glucose uptake, storage and metabolism. We demonstrated that the restoring effect of vitamin D 3 is mediated through VDR modulation, thereby improving signal transduction and controlling free radicals in the liver of diabetic rats. These data suggest a potential role for vitamin D 3 in the treatment of diabetes-associated hepatic complications.Key words: Vitamin D: Diabetes: Liver: Oxidative stress: Metabolism: Insulin Diabetes-associated complications are major causes of morbidity and mortality. The liver plays a unique role in glucose homeostasis. Because of its anatomical location, it is ideally suited to control the systemic supply of absorbed nutrients, and it is one of only two organs that both consume and produce substantial amounts of glucose. The central role of the liver in the maintenance of blood glucose levels is assured by complex regulation by metabolic substrates, insulin and other hormones (1) . Diabetes-associated hyperglycaemia and hypoinsulinaemia lead to the impairment of hepatic glucose and lipid metabolism. Virtually, the entire spectrum of liver diseases is seen in patients with diabetes, including liver cirrhosis, a significant cause of death in diabetic patients, even more relevant than CVD (2) . Interest in the development of novel antidiabetic agents has been fuelled by the intense complications due to therapeutic treatment of diabetes and associated liver failure (2,3) . An increased prevalence of diabetes has been observed in vitamin D-deficient individuals (4) , and our previous study has shown that vitamin D 3 treatment restores blood glucose homeostasis in streptozotocin (STZ)-induced diabetic rats (5) . Bind...

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Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-κB

Cited by 170 publications

References 50 publications

Curcumin suppresses transforming growth factor-β1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways

Curcumin suppresses transforming growth factor-β1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

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Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-κB

Cited by 170 publications

References 50 publications

Curcumin suppresses transforming growth factor-β1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways

Curcumin suppresses transforming growth factor-β1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes

Effect of vitamin D3in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

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Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats