Abstract
Abnormal activation of nuclear factor kappa B (NF-kappaB) probably plays an important role in the pathogenesis of Duchenne's muscular dystrophy (DMD). In this report, we evaluated the efficacy of curcumin, a potent NF-kappaB inhibitor, in mdx mice, a mouse model of DMD. We found that it improved sarcolemmic integrity and enhanced muscle strength after intraperitoneal (i.p.) injection. Histological analysis revealed that the structural defects of myofibrils were reduced, and biochemical analysis showed that creatine kinase (CK) activity was decreased. We also found that levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in the mdx mice were decreased by curcumin administration. EMSA analysis showed that NF-kappaB activity was also inhibited. We thus conclude that curcumin is effective in the therapy of muscular dystrophy in mdx mice, and that the mechanism may involve inhibition of NF-kappaB activity. Since curcumin is a non-toxic compound derived from plants, we propose that it may be useful for DMD therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Creatine Kinase / antagonists & inhibitors
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Creatine Kinase / blood
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Curcumin / administration & dosage
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Humans
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Injections, Intraperitoneal
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / blood
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Mice
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Mice, Inbred C57BL
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Mice, Inbred mdx
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Muscle Strength / drug effects*
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Muscle Strength / physiology
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiology*
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Muscular Dystrophy, Animal / drug therapy*
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Muscular Dystrophy, Animal / pathology
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Muscular Dystrophy, Animal / physiopathology
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Muscular Dystrophy, Duchenne / drug therapy
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NF-kappa B / antagonists & inhibitors*
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Nitric Oxide Synthase Type II / biosynthesis
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Nitric Oxide Synthase Type II / genetics
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Phytotherapy*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / blood
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Interleukin-1beta
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NF-kappa B
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Tumor Necrosis Factor-alpha
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Nitric Oxide Synthase Type II
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Creatine Kinase
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Curcumin