Curcumin Inhibits Transforming Growth Factor-β Activity via Inhibition of Smad Signaling in HK-2 Cells

Hu, Ying; Hua, Liang; Du, Yong; Zhu, Yong-Liang; Wang, Xuanding

doi:10.1159/000287230

Cited by 37 publications

(26 citation statements)

References 79 publications

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“…As a matter of fact, we did find a significant inhibition effect of 50 mM curcumin prior to 12 h. Finally, despite its cytoprotective effect, 26) curcumin was recently found to be cytotoxic against HK-2 cells at 50 mM. 27) Although no clear evidence supported the possible positive effect of curcumin on the synthesis, sorting and secretion of these two proteins, the relatively higher concentration of curcumin used herein should be considered when explaining these results. On the other hand, the fact that 5 mM curcumin showed a limited inhibition effect against MCP-1 and IL-8 secretion might be due to the relatively lower concentration.…”

Section: Effects Of Curcumin On the Secretion Of Il-8 In Lps-mentioning

confidence: 52%

Curcumin Attenuates Lipopolysaccharide-Induced Renal Inflammation

Zhong

Chen

Lin

et al. 2011

Biological & Pharmaceutical Bulletin

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Curcumin is a bright yellow compound found in turmeric, which is derived from the rhizomes of the plant Curcuma longa LINN, a perennial herb of the Zingerberaceae family. 1) It has been used for millennia as a wound-healing agent and for treating a large number of diseases in traditional Chinese and Indian medicine.2) A wide variety of cellular properties of curcumin have been demonstrated, including anti-inflammatory, antioxidant, antiproliferative, pro-apoptotic, anti-bacterial and anti-cancer activities.3) Among all these biological activities, the anti-inflammatory effects of curcumin have been assessed in various in vitro systems and in experimental animal systems. 4,5) Renal inflammation is the main pathological change in many acute and chronic kidney diseases. Several studies have demonstrated that curcumin played a positive role in inflammation-related renal injury using various animal models, 6-10) of which only one study used cultured cell lines as the in vitro model. 10) Lipopolysaccharide (LPS), the product of Gram-negative bacteria, is an important inflammatory factor and has been widely used to induce renal inflammation models when studying inflammation-related renal diseases. [11][12][13] This model was also employed in the present study to investigate the effect of curcumin on renal inflammation. In a variety of acute and chronic renal inflammation, renal tubular epithelial cells were not only the victims, but also actively participate in the process of glomerular sclerosis and renal fibrosis by secreting a variety of inflammatory chemokines and extracellular matrix. Considering the important role renal tubular epithelial cells played in renal inflammation, a human proximal tubule cell line (HK-2 cells) was selected as the in vitro model. By using both in vitro and in vivo models, we attempted to obtain an allaround evaluation of curcumin on renal inflammation, and also gain a preliminary view of the underlying mechanism. MATERIALS AND METHODSChemicals Keratinocyte-serum-free medium (SFM) cell culture medium, fetal bovine serum, trypsin, and Trizol RNA extraction reagent were purchased from Gibco Life Technologies, Inc. .).Cell Culture HK-2 cells, an immortalized proximal tubular epithelial cell (PTEC) line from normal adult human kidney, were obtained from the American Type Culture Collection (Manassas, VA, U.S.A.). HK-2 cells were cultured in Keratinocyte-SFM cell culture medium containing 2% fetal calf serum at 37°C and 5% CO 2 .Animals Kunming mice of specific pathogen free (SPF) level (6-8 weeks old), ranging from 18 to 22 g, were purchased from the Laboratory Animal Center of Shanghai Jiao Tong University (Shanghai, China). The animals were maintained under climate-controlled conditions with a 12-h light/dark cycle, and were fed standard rodent chow and water. The guidelines for the care of the animals were strictly The present study demonstrated that curcumin has a protective effect on LPS-induced experimental renal inflammation, and this effect might be attributed to its inhibitory effec...

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Section: Effects Of Curcumin On the Secretion Of Il-8 In Lps-mentioning

confidence: 52%

Curcumin Attenuates Lipopolysaccharide-Induced Renal Inflammation

Zhong

Chen

Lin

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Beta-adrenergic receptor was an important protein of calcium signaling pathway. Quercetin and curcumin regulate beta-adrenergic receptor, which lead to a reduction in angiotensin II, α1 adrenergic receptors vasoconstriction and tubular sodium reabsorption [92], [93], [143], [144].…”

Section: Resultsmentioning

confidence: 99%

“…5. As shown in the figure, tanshinone IIA and curcumin can jointly act on TGFB1 to downregulate the expression of TGFB and to reduce the deposit of extracellular matrix (ECM) [144], [148]. Quercetin and rhein can jointly act on PTPN1; tanshinone IIA and rhein can jointly act on FYN and LCK.…”

Section: Resultsmentioning

confidence: 99%

A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease

Shi

Cai

et al. 2014

PLoS ONE

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Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM.

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“…To assess activated TGF-β1 signalling in liver tissue, we assayed total Smad2 and Smad2 phosphorylation, finding that curcumin inhibited both total and phosphorylated Smad2. Curcumin has been shown to block the profibrotic activities of TGFβ on human proximal tubule cells in vitro , by down-regulating the Smad signalling pathway, suggesting that curcumin may have effects similar to those of serine/threonine protein phosphatases [38]. Moreover, prolonged curcumin treatment in vivo was found to significantly reduce TβRII levels and Smad2/3 phosphorylation in response to added TGF-β [33].…”

Section: Discussionmentioning

confidence: 99%

Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats

Yao

Wang

et al. 2012

BMC Complement Altern Med

104

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BackgroundAt present there is no effective and accepted therapy for hepatic fibrosis. Transforming growth factor (TGF)-β1 signaling pathway contributes greatly to hepatic fibrosis. Reducing TGF-β synthesis or inhibiting components of its complex signaling pathway represent important therapeutic targets. The aim of the study was to investigate the effect of curcumin on liver fibrosis and whether curcumin attenuates the TGF-β1 signaling pathway.MethodsSprague–Dawley rat was induced liver fibrosis by carbon tetrachloride (CCl4) for six weeks together with or without curcumin, and hepatic histopathology and collagen content were employed to quantify liver necro-inflammation and fibrosis. Moreover, the mRNA and protein expression levels of TGF-β1, Smad2, phosphorylated Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF) were determined by quantitative real time-PCR, Western blot, or immunohistochemistry.ResultsRats treated with curcumin improved liver necro-inflammation, and reduced liver fibrosis in association with decreased α-smooth muscle actin expression, and decreased collagen deposition. Furthermore, curcumin significantly attenuated expressions of TGFβ1, Smad2, phosphorylated Smad2, Smad3, and CTGF and induced expression of the Smad7.ConclusionsCurcumin significantly attenuated the severity of CCl4-induced liver inflammation and fibrosis through inhibition of TGF-β1/Smad signalling pathway and CTGF expression. These data suggest that curcumin might be an effective antifibrotic drug in the prevention of liver disease progression.

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Curcumin Inhibits Transforming Growth Factor-β Activity via Inhibition of Smad Signaling in HK-2 Cells

Cited by 37 publications

References 79 publications

Curcumin Attenuates Lipopolysaccharide-Induced Renal Inflammation

Curcumin Attenuates Lipopolysaccharide-Induced Renal Inflammation

A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease

Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats

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