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      Curcumin prevents muscle damage by regulating NF-κB and Nrf2 pathways and improves performance: an in vivo model

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          Abstract

          Purpose

          Exercise (Ex) increases reactive oxygen species and impairs antioxidant defense systems. Recent data suggest that curcumin (CW) possesses peroxisome proliferator-activated receptor gamma activity and anti-inflammatory properties. Therefore, this study was designed to investigate the effects of CW supplementation on Ex performance, endurance, and changes in serum and muscle proteins in rats after exhaustive Ex.

          Materials and methods

          Twenty-eight (28) male Wistar rats (age: 8 weeks and body weight: 180±20 g) were divided into four treatment groups: 1) control (C; no Ex), 2) C + CW (no Ex + CW), 3) C + Ex, and 4) C + Ex + CW (Ex + CW). CW was administered as 100 mg/kg CurcuWin ®, providing 20 mg of curcuminoids daily for 6 weeks. A motor-driven rodent treadmill was used to carry out the Ex protocols. During a 5-day period, animals in chronic Ex groups were put through different regimens: day 1, 10 m/min for 10 minutes; day 2, 20 m/min for 10 minutes; day 3, 25 m/min for 10 minutes; day 4, 25 m/min for 20 minutes; and day 5, 25 m/min for 30 minutes. Animals were exercised at 25 m/min for 45 min/d for 5 d/wk for 6 weeks. Blood and muscle samples were analyzed for muscle markers, oxidative stress, and antioxidant markers.

          Results

          Lactate and muscle malondialdehyde levels decreased in the CW-treated groups ( P<0.0001). However, activities of antioxidant enzyme levels increased in the CW-treated groups. Run to exhaustion (minutes) improved in the CW-treated groups. Muscle nuclear factor-κB ( P<0.05) and heat shock protein 70 ( P<0.05) levels were much lowered in the CW treated group followed by Ex group. In addition, muscle inhibitors of kappa B, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, thioredoxin-1, sirtuin 1, nuclear factor (erythroid-derived 2)-like 2, and glucose transporter 4 protein levels in the Ex + CW group were higher than those in the control and Ex groups ( P<0.05).

          Conclusion

          This study suggests that novel CW has the potential to help prevent muscle damage by regulating the nuclear factor-κB and nuclear factor (erythroid-derived 2)-like 2 pathways and improve the performance and nutritional values of CW.

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          Most cited references39

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          Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals.

          Extensive research within the past two decades has revealed that obesity, a major risk factor for type 2 diabetes, atherosclerosis, cancer, and other chronic diseases, is a proinflammatory disease. Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance.
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            Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG.

            Frequent consumption of green tea, one of the most popular and widely consumed beverages, has been known to protect against development of various cancers according to numerous experimental and several population-based studies. Molecular mechanisms underlying chemopreventive effects exerted by green tea and its components have been extensively investigated. (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to induce expression of glutathione S-transferase, glutathione peroxidase, glutamate cysteine ligase, hemeoxygenase-1, etc. that are involved in the elimination or inactivation of reactive oxygen species and electrophiles implicated in multi-stage carcinogenesis. The redox-sensitive transcription factor, nuclear factor erythroid 2 p45 (NF-E2)-related factor (Nrf2) plays a key role in regulating induction of phase II detoxifying or antioxidant enzymes. Thus, activation of Nrf2 is considered to be an important molecular target of many chemopreventive and chemoprotective agents. This review summarizes the molecular basis of chemoprevention and cytoprotection afforded by EGCG with emphasis on its ability to modulate Nrf2-mediated cellular events.
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              Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers.

              TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000-20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.
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                Author and article information

                Journal
                J Inflamm Res
                J Inflamm Res
                Journal of Inflammation Research
                Journal of Inflammation Research
                Dove Medical Press
                1178-7031
                2016
                29 August 2016
                : 9
                : 147-154
                Affiliations
                [1 ]Department of Animal Nutrition, Faculty of Veterinary Medicine
                [2 ]Department of Movement and Training Science
                [3 ]Department of Biology, Firat University, Elazig, Turkey
                [4 ]OmniActive Health Technologies Inc., Morristown, NJ, USA
                Author notes
                Correspondence: Vijaya Juturu, OmniActive Health Technologies Inc., 67 East Park Place, Morristown, NJ 07960, USA, Email v.juturu@ 123456omniactives.com
                Article
                jir-9-147
                10.2147/JIR.S110873
                5010171
                27621662
                bbc3fac0-2c40-4264-b0d0-0b394201d780
                © 2016 Sahin et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Immunology
                exercise,curcumin,oxidative stress,nf-kb,nrf2,muscle
                Immunology
                exercise, curcumin, oxidative stress, nf-kb, nrf2, muscle

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