A soft coral-derived compound, 11-epi-sinulariolide acetate suppresses inflammatory response and bone destruction in adjuvant-induced arthritis

• Published in: PloS one 2013-05, Vol.8 (5), p.e62926
• Main Authors: Lin, Yen-You, Jean, Yen-Hsuan, Lee, Hsin-Pai, Chen, Wu-Fu, Sun, Yu-Min, Su, Jui-Hsin, Lu, Yi, Huang, Shi-Ying, Hung, Han-Chun, Sung, Ping-Jyun, Sheu, Jyh-Horng, Wen, Zhi-Hong
• Format: Article
• Language: English
• Subjects: Acetates; Acetic acid; Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid Phosphatase - antagonists & inhibitors; Acid Phosphatase - genetics; Acid Phosphatase - metabolism; Acid resistance; Animal experimentation; Animal research; Animal tissues; Animals; Ankle; Anthozoa - chemistry; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Biology; Biotechnology; Bone Resorption - prevention & control; Bone surgery; Cathepsin K; Cathepsin K - antagonists & inhibitors; Cathepsin K - genetics; Cathepsin K - metabolism; Cathepsins; Chemical compounds; Chemistry; Clinical trials; Corals; COX-2 inhibitors; Cyclooxygenase-2; Cytokines; Diterpenes - isolation & purification; Diterpenes - pharmacology; Drug Administration Schedule; Edema; Female; Fibroblasts; Gelatinase B; Gene Expression - drug effects; Hindlimb - drug effects; Hindlimb - immunology; Hindlimb - pathology; Hospitals; Inflammation; Inflammation - prevention & control; Inflammatory response; Injections, Subcutaneous; Isoenzymes - antagonists & inhibitors; Isoenzymes - genetics; Isoenzymes - metabolism; Lipopolysaccharides; Macrophages; Marine biology; Marine organisms; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Medical research; Medicine; Metabolites; Mitogens; Museums; Neutrophils; Nitric oxide; Nitric-oxide synthase; Orthopedics; Pharmacology; Phosphatase; Proteins; Rats; Rats, Inbred Lew; Rheumatoid arthritis; Rheumatoid factor; Rodents; Sinularia querciformis; Sinulariolide; Studies; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0062926

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.