title: A soft coral-derived compound, 11-epi-sinulariolide acetate suppresses inflammatory response and bone destruction in adjuvant-induced arthritis.
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.
authors.affiliation: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan, Republic of China.
authors.forename: Yen-You
authors.initials: YY
authors.lastname: Lin
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Jean
authors.forename: Hsin-Pai
authors.initials: HP
authors.lastname: Lee
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Sun
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.forename: Han-Chun
authors.initials: HC
authors.lastname: Hung
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001862:Bone Resorption / Q000517:prevention & control*; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000517:prevention & control; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; C050253:sinulariolide; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534133:Ctsk protein, rat; D020780:Matrix Metalloproteinase 9