A marine fungus-derived nitrobenzoyl sesquiterpenoid suppresses receptor activator of NF-kappa B ligand-induced osteoclastogenesis and inflammatory bone destruction
文献类型：期刊论文
| 作者 | Tan, Yanhui1; Deng, Wende1; Zhang, Yueyang1; Ke, Minhong1; Zou, Binhua1; Luo, Xiaowei2; Su, Jianbin1; Wang, Yiyuan1; Xu, Jialan1; Nandakumar, Kutty Selva1 |
| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2020 |
| 卷号 | 177期号:18页码:4242 |
| 关键词 | DC-STAMP NF-kappa B NFATc1 nitrobenzoyl sesquiterpenoids osteoclast osteolysis |
| ISSN号 | 0007-1188 |
| DOI | 10.1111/bph.15179 |
| 英文摘要 | Background and Purpose: Osteoclasts are unique cells to absorb bone. Targeting osteoclast differentiation is a therapeutic strategy for osteolytic diseases. Natural marine products have already become important sources of new drugs. The naturally occurring nitrobenzoyl sesquiterpenoids first identified from marine fungi in 1998 are bioactive compounds with a special structure, but their pharmacological functions are largely unknown. Here, we investigated six marine fungus-derived nitrobenzoyl sesquiterpenoids on osteoclastogenesis and elucidated the mechanisms. Experimental Approach: Compounds were first tested by RANKL-induced NF-kappa B luciferase activity and osteoclastic TRAP assay, followed by molecular docking to characterize the structure-activity relationship. The effects and mechanisms of the most potent nitrobenzoyl sesquiterpenoid on RANKL-induced osteoclastogenesis and bone resorption were further evaluated in vitro. Micro-CT and histology analysis were used to assess the prevention of bone destruction by nitrobenzoyl sesquiterpenoids in vivo. Key Results: Nitrobenzoyl sesquiterpenoid 4, with a nitrobenzoyl moiety at C-14 and a hydroxyl group at C-9, was the most active compound on NF-kappa B activity and osteoclastogenesis. Consequently, nitrobenzoyl sesquiterpenoid 4 exhibited suppression of RANKL-induced osteoclastogenesis and bone resorption from 0.5 mu M. It blocked RANKL-induced I kappa Ba phosphorylation, NF-kappa B p65 and RelB nuclear translocation, NFATc1 activation, reduced DC-STAMP but not c-Fos expression during osteoclastogenesis in vitro. Nitrobenzoyl sesquiterpenoid 4 also ameliorated LPS-induced osteolysis in vivo. Conclusion and Implications: These results highlighted nitrobenzoyl sesquiterpenoid 4 as a novel inhibitor of osteoclast differentiation. This marine-derived sesquiterpenoid is a promising lead compound for the treatment of osteolytic diseases. |
| 资助机构 | National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773740, 81741154, 81073119]; Guangzhou Science and Technology Plan Project [201804010027]; Pearl River S&T Nova Program of Guangzhou Scientific Research Project [201610010017] ; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773740, 81741154, 81073119]; Guangzhou Science and Technology Plan Project [201804010027]; Pearl River S&T Nova Program of Guangzhou Scientific Research Project [201610010017] |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/18370]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 作者单位 | 1.Southern Med Univ, Sch Pharmaceut Sci, Lab Antiinflammatory & Immunomodulatory Pharmacol, Guangzhou, Peoples R China 2.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China 3.Chinese Acad Sci, Guangdong Key Lab Marine Mat Med, CAS Key Lab Trop Marine Bioresources & Ecol, South China Sea Inst Oceanol, Guangzhou 510301, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tan, Yanhui,Deng, Wende,Zhang, Yueyang,et al. A marine fungus-derived nitrobenzoyl sesquiterpenoid suppresses receptor activator of NF-kappa B ligand-induced osteoclastogenesis and inflammatory bone destruction[J]. BRITISH JOURNAL OF PHARMACOLOGY,2020,177(18):4242, 4260. |
| APA | Tan, Yanhui.,Deng, Wende.,Zhang, Yueyang.,Ke, Minhong.,Zou, Binhua.,...&Li, Xiaojuan.(2020).A marine fungus-derived nitrobenzoyl sesquiterpenoid suppresses receptor activator of NF-kappa B ligand-induced osteoclastogenesis and inflammatory bone destruction.BRITISH JOURNAL OF PHARMACOLOGY,177(18),4242. |
| MLA | Tan, Yanhui,et al."A marine fungus-derived nitrobenzoyl sesquiterpenoid suppresses receptor activator of NF-kappa B ligand-induced osteoclastogenesis and inflammatory bone destruction".BRITISH JOURNAL OF PHARMACOLOGY 177.18(2020):4242. |
入库方式： OAI收割
来源：南海海洋研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。