Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan, Republic of China.
PLoS One. 2013 May 13;8(5):e62926. doi: 10.1371/journal.pone.0062926. Print 2013.
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.
近年来,从海洋生物中发现了大量具有强大抗炎特性的代谢物,其中一些化合物目前正在临床试验中。在本研究中,我们从 Formosa 软珊瑚 Sinularia querciformis 中分离出具有抗炎作用的 cembrane 型化合物 11-epi-sinulariolide acetate(Ya-s11)。初步筛选表明,Ya-s11 可显著抑制脂多糖刺激的小鼠巨噬细胞中诱导型一氧化氮合酶和环氧化酶-2 的表达。我们还研究了 Ya-s11 对雌性 Lewis 大鼠佐剂性关节炎(AIA)的治疗作用,AIA 大鼠表现出类似于人类类风湿关节炎(RA)的特征。动物实验表明,Ya-s11(从免疫后第 7 天至第 28 天每隔 2 天皮下注射 9 mg/kg 一次)可显著抑制 AIA 特征。此外,Ya-s11 还可减轻 AIA 大鼠踝关节组织中组织蛋白酶 K、基质金属蛋白酶-9(MMP-9)、抗酒石酸酸性磷酸酶(TRAP)和肿瘤坏死因子-α(TNF-α)的蛋白表达。基于其对 AIA 大鼠中促炎蛋白表达和疾病进展的抑制作用,这种源自海洋的化合物 Ya-s11 可能成为治疗 RA 的有效治疗剂。