Curcumin in inflammatory diseases

School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
BioFactors (Impact Factor: 3). 01/2013; 39(1). DOI: 10.1002/biof.1066
Source: PubMed

ABSTRACT Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. © 2012 BioFactors, 2013.

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    ABSTRACT: Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and anti-inflammatory properties. To study the effectiveness of supplementation with a bioavailable curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma C-reactive protein (CRP) concentrations. In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to curcuminoids (n = 59; drop-outs = 9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis. Supplementation with curcuminoid-piperine combination significantly improved serum SOD activities (p < 0.001) and reduced MDA (p < 0.001) and CRP (p < 0.001) concentrations compared with placebo. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo in reducing circulating CRP concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis. Short-term supplementation with curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
    Clinical Nutrition 01/2015; DOI:10.1016/j.clnu.2014.12.019 · 3.94 Impact Factor
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    ABSTRACT: We have previously reported that curcumin analogs with a C7 linker bearing a C4-C5 olefinic linker with a single keto group at C3 (enone linker) display mid-nanomolar activity against the bloodstream form of Trypanosoma brucei. However, no clear indication of their mechanism of action, or of their superior antiparasitic activity relative to analogs with the original di-ketone curcumin linker, was apparent. In order to further investigate their utility as antiparasitic agents, we here compare the cellular effects of curcumin and the enone linker lead compound, AS-HK014. An AS-HK014-resitant line, TA014, was developed by in vitro exposure to the drug. Metabolomic analysis revealed that exposure to AS-HK014, but not curcumin, rapidly depleted glutathione and trypanothione in the wild-type line, although almost all other metabolites were unchanged relative to control. In TA014 cells thiol levels were similar to untreated wild-type cells, and were not significantly depleted by AS-HK014. Adducts of AS-HK014 with both glutathione and trypanothione were identified in AS-HK014-exposed wild-type cells, and reproduced by chemical reaction. However, adduct accumulation in sensitive cells was much lower than in resistant cells. TA014 cells did not exhibit any changes in sequence or protein levels of glutathione synthetase and γ-glutamylcysteine synthetase relative to wild-type cells. We conclude that mono-enone curcuminoids have a different mode of action than curcumin, rapidly and specifically depleting thiol levels in trypanosomes by forming an adduct. This adduct may ultimately be responsible for the highly potent trypanocidal activity antiparasitic activity of the mono-enone curcuminoids. The American Society for Pharmacology and Experimental Therapeutics.
    Molecular pharmacology 12/2014; DOI:10.1124/mol.114.096016 · 4.12 Impact Factor
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    ABSTRACT: ABSTRACT Oxidative stress is implicated in the pathogenesis of osteoarthritis. Curcuminoids are natural polyphenols with strong antioxidant capacity and may thus be helpful in the treatment of osteoarthritis. The present randomized double-blind placebo-controlled trial investigated the efficacy of curcuminoids in reducing systemic oxidative burden in patients suffering from knee osteoarthritis. Forty patients with mild-to-moderate primary knee osteoarthritis were given curcuminoid capsules (1500 mg/day in 3 divided doses; n = 19) or matched placebo capsules (n = 21) for a period of 6 weeks. Curcuminoids were co-administered with piperine (15 mg/day) in order to improve the bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and malonedialdehyde (MDA) were determined spectrophotometrically at baseline and at the end of the treatment period in both groups. Serum activities of SOD as well as GSH and MDA concentrations were comparable between the study groups at baseline (p > 0.05). There was a significant elevation in serum SOD activities (mean change: 2.94 ± 3.73 vs. -0.38 ± 1.33; p < 0.001), a borderline significant elevation in GSH concentrations (mean change: 1.39 ± 2.78 vs. -0.02 ± 1.62; p = 0.064) and a significant reduction in MDA concentrations (mean change: -5.26 ± 4.46 vs. -2.49 ± 3.81; p = 0.044) in the curcuminoids compared with the placebo group. Changes in serum activities of SOD and concentrations of GSH and MDA during the course of trial were significantly correlated. Short-term supplementation with curcuminoids attenuates systemic oxidative stress in patients with osteoarthritis. These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms.
    Journal of Dietary Supplements 02/2015; DOI:10.3109/19390211.2015.1008611


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Jan 7, 2015