Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes

Wang, Mu-En; Chen, Yi‐Chen; Chen, I-Shu; Hsieh, Shu-Chen; Chen, Sheng-Shih; Chiu, Chien Chao

doi:10.1016/j.jnutbio.2011.08.004

Cited by 97 publications

(59 citation statements)

References 37 publications

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“…Curcumin protects hepatocytes against cellular damages induced by radiation 9 and oxidative stress, [10][11][12] and induces apoptosis of damaged hepatocytes. 13 We demonstrate that curcumin reduces liver fibrosis by attenuating oxidative stress, suppressing inflammation, 14 and inhibiting pathological angiogenesis. 15 Curcumin also inhibits HSC activation associated with interruption of transforming growth factor-β 16 and plateletderived growth factor pathways.…”

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confidence: 76%

Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells

Lian

Jiang

Zhang

et al. 2015

Laboratory Investigation

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Accumulating evidence indicates that Hedgehog (Hh) signaling becomes activated in chronic liver injury and plays a role in the pathogenesis of hepatic fibrosis. Hepatic stellate cells (HSCs) are Hh-responsive cells and activation of the Hh pathway promotes transdifferentiation of HSCs into myofibroblasts. Targeting Hh signaling may be a novel therapeutic strategy for treatment of liver fibrosis. We previously reported that curcumin has potent antifibrotic effects in vivo and in vitro, but the underlying mechanisms are not fully elucidated. This study shows that curcumin downregulated Patched and Smoothened, two key elements in Hh signaling, but restored Hhip expression in rat liver with carbon tetrachlorideinduced fibrosis and in cultured HSCs. Curcumin also halted the nuclear translocation, DNA binding, and transcription activity of Gli1. Moreover, the Hh signaling inhibitor cyclopamine, like curcumin, arrested the cell cycle, induced mitochondrial apoptosis, reduced fibrotic gene expression, restored lipid accumulation, and inhibited invasion and migration in HSCs. However, curcumin's effects on cell fate and fibrogenic properties of HSCs were abolished by the Hh pathway agonist SAG. Furthermore, curcumin and cyclopamine decreased intracellular levels of adenosine triphosphate and lactate, and inhibited the expression and/or function of several key molecules controlling glycolysis. However, SAG abrogated the curcumin effects on these parameters of glycolysis. Animal data also showed that curcumin downregulated glycolysis-regulatory proteins in rat fibrotic liver. These aggregated data therefore indicate that curcumin modulated cell fate and metabolism by disrupting the Hh pathway in HSCs, providing novel molecular insights into curcumin reduction of HSC activation.

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confidence: 76%

Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells

Lian

Jiang

Zhang

et al. 2015

Laboratory Investigation

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“…Curcumin has a myriad of pharmacological effects, including anti-inflammatory (13,14), anti-bacterial (15), anti-oxidative (16) and renal-protective activities (17,18). A previous study suggested that curcumin has a therapeutic role in a rat model of SAP (19).…”

Section: Introductionmentioning

confidence: 99%

Curcumin protects against acute renal injury by suppressing JAK2/STAT3 pathway in severe acute pancreatitis in rats

Zhu

Zhang

Weng

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the effect of curcumin on acute renal injury in a rat model of severe acute pancreatitis (SAP). A SAP model with acute kidney injury was established in rats by retrograde injection of 5% sodium taurocholate into the pancreatic duct. The serum amylase, creatinine (Cr) and blood urea nitrogen (BUN) levels in rats were measured. Hematoxylin and eosin staining was used to assess pancreatic and renal histological changes. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured using ELISA kits. Renal protein levels of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway components were determined by western blot assay. The results showed that curcumin significantly decreased serum amylase, Cr and BUN levels, and alleviated pancreatic and renal histological changes in SAP rats. Furthermore, curcumin markedly decreased serum TNF-α and IL-6 levels and downregulated renal protein levels of JAK2/STAT3 pathway components. These results proved that curcumin ameliorates acute renal injury in a rat model of SAP. The molecular mechanism of its effect may be associated with the suppression of the JAK2/STAT3 pathway to reduce TNF-α and IL-6 levels in SAP-induced acute renal injury. Therefore, the findings of the present study revealed the potential use of curcumin for the prevention and treatment of SAP and the associated renal injury. IntroductionSevere acute pancreatitis (SAP), an acute inflammatory condition of the pancreas, is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute renal injury (ARI) is one of the main complications of SAP and significantly increases the mortality rate of patients with AP (66.6 vs. 14.5%) (1). However, the underlying mechanisms of ARI occurring in patients with SAP have remained to be clarified. Increasing evidence has indicated that pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, have an important role in the pathological mechanisms of SAP and SAP-associated organ failure (2-4). Therefore, inhibiting the transcription and translation of mediators to reduce the secretion of pro-inflammatory factors may ameliorate inflammation and renal failure in SAP.Signal transducers and activators of transcription (STATs), a protein family comprised of seven members (STAT1, -2, -3, -4, -5a, -5b and -6), generally transduce signals from activated receptors or intracellular kinases to the nucleus, thus activating and regulating gene transcription (5). The Janus kinase 2 (JAK2)/STAT3 pathway is well known to be involved in the immune response of numerous cytokines, including TNF-α and IL-6 (6). In addition, evidence derived from numerous clinical and experimental studies suggests the involvement of the JAK2/STAT3 pathway in pancreatitis (7-9) or renal diseases (10-12).Curcumin (diferuloylmethane), the active phytochemical component of turmeric (a spice used mostly in Asia) h...

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“…Pretreatment with CMN and QR was found to modulate mitochondrial dysfunction in rodents, and its property as an antioxidant is widely held to be responsible for its protective effects in the mitochondria (Carrasco-Pozo et al 2012;Sood et al 2011). The compound has been described to possess a variety of pharmacological and biological activities including anti-inflammatory (Dai et al 2013;Wang et al 2012), antimicrobial (Kallio et al 2012), antioxidant (Waseem and Parvez 2013;Tang et al 2012), and anticancer activities (Youn et al 2013;Sarkar et al 2010). The mitochondria are the main target for many anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin

Waseem

Parvez

2015

Protoplasma

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Peripheral neurotoxicity is one of the serious dose-limiting side effects of oxaliplatin (Oxa) when used in the treatment of malignant conditions. It is documented that it elicits major side effects specifically neurotoxicity due to oxidative stress forcing the patients to limit its clinical use in long-term treatment. Oxidative stress has been proven to be involved in Oxa-induced toxicity including neurotoxicity. The mitochondria have recently emerged as targets for anticancer drugs in various kinds of toxicity including neurotoxicity that can lead to neoplastic disease. However, there is paucity of literature involving the role of the mitochondria in mediating Oxa-induced neurotoxicity and its underlying mechanism is still debatable. The purpose of this study was to investigate the dose-dependent damage caused by Oxa on isolated brain mitochondria under in vitro conditions. The study was also designed to investigate the neuroprotective effects of nutraceuticals, curcumin (CMN), and quercetin (QR) on Oxa-induced mitochondrial oxidative stress and respiratory chain complexes in the brain of rats. Oxidative stress biomarkers, levels of nonenzymatic antioxidants, activities of enzymatic antioxidants, and mitochondrial complexes were evaluated against the neurotoxicity induced by Oxa. Pretreatment with CMN and QR significantly replenished the mitochondrial lipid peroxidation levels and protein carbonyl content induced by Oxa. CMN and QR ameliorated altered nonenzymatic and enzymatic antioxidants and complex enzymes of mitochondria. We conclude that CMN and QR, by attenuating oxidative stress as evident by mitochondrial dysfunction, hold promise as agents that can potentially reduce Oxa-induced adverse effects in the brain.

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Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes

Cited by 97 publications

References 37 publications

Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells

Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells

Curcumin protects against acute renal injury by suppressing JAK2/STAT3 pathway in severe acute pancreatitis in rats

Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin

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