Abstract
In recent years, a significant number of metabolites with potent anti-inflammatory properties have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we isolated 11-epi-sinulariolide acetate (Ya-s11), a cembrane-type compound with anti-inflammatory effects, from the Formosa soft coral Sinularia querciformis. Preliminary screening revealed that Ya-s11 significantly inhibited the expression of the proinflammatory proteins induced nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated murine macrophages. We also examined the therapeutic effects of Ya-s11 on adjuvant-induced arthritis (AIA) in female Lewis rats, which demonstrate features similar to human rheumatoid arthritis (RA). Animal experiments revealed that Ya-s11 (subcutaneously 9 mg/kg once every 2 days from day 7 to day 28 postimmunization) significantly inhibited AIA characteristics. Moreover, Ya-s11 also attenuated protein expression of cathepsin K, matrix metalloproteinases-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor-α (TNF-α) in ankle tissues of AIA-rats. Based on its attenuation of the expression of proinflammatory proteins and disease progression in AIA rats, the marine-derived compound Ya-s11 may serve as a useful therapeutic agent for the treatment of RA.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acid Phosphatase / antagonists & inhibitors
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Acid Phosphatase / genetics
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Acid Phosphatase / metabolism
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Animals
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Anthozoa / chemistry*
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Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Arthritis, Experimental / drug therapy*
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Arthritis, Experimental / immunology
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Arthritis, Experimental / pathology
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Bone Resorption / prevention & control*
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Cathepsin K / antagonists & inhibitors
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Cathepsin K / genetics
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Cathepsin K / metabolism
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Diterpenes / isolation & purification
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Diterpenes / pharmacology*
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Drug Administration Schedule
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Female
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Gene Expression / drug effects
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Hindlimb / drug effects*
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Hindlimb / immunology
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Hindlimb / pathology
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Inflammation / prevention & control
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Injections, Subcutaneous
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Rats
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Rats, Inbred Lew
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Tartrate-Resistant Acid Phosphatase
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Diterpenes
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Isoenzymes
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Tumor Necrosis Factor-alpha
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sinulariolide
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Acid Phosphatase
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Tartrate-Resistant Acid Phosphatase
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Cathepsin K
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Ctsk protein, rat
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Matrix Metalloproteinase 9
Grants and funding
This work was supported, in part, by grants from the National Science Council, Taiwan (NSC100-2325-B-110-001 and NSC99-2313-B110-003-MY03), and Pingtung Christian Hospital, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.