中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Ainsliadimer C, a disesquiterpenoid isolated from Ainsliaea macrocephala, ameliorates inflammatory responses in adipose tissue via Sirtuin 1-NLRP3 inflammasome axis

文献类型：期刊论文

作者Chen, Cheng1; Ren, Yong-mei2; Zhu, Jian-zhong1; Chen, Jia-li1; Feng, Zhe-ling1; Zhang, Tian1; Ye, Yang2; Lin, Li-gen1
刊名ACTA PHARMACOLOGICA SINICA
出版日期2021-11-17
页码13
关键词Ainsliadimer C interleukin-1 beta macrophages NLRP3 inflammasome Sirtuin 1 adipose tissue inflammation obesity metabolic disorders EX-527 dexamethasone
ISSN号1671-4083
DOI10.1038/s41401-021-00797-z
通讯作者Ye, Yang(yye@simm.ac.cn) ; Lin, Li-gen(ligenl@um.edu.mo)
英文摘要Interleukin-1 beta (IL-1 beta), a key pro-inflammatory cytokine, is majorly produced by macrophages through NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, which has been identified as the culprit to deteriorate the inflammatory crosstalk between macrophages and adipocytes. Ainsliadimer C (AC) is a disesquiterpenoid isolated from Ainsliaea macrocephala. In the current study, we investigated the effects of AC on adipose tissue inflammation in co-culture of macrophages and adipocytes in vitro as well as in LPS-treated mice in vivo. We showed that AC (20-80 mu M) dose-dependently inhibited the secretion of IL-1 beta from LPS plus ATP-stimulated THP-1 macrophages by inhibiting the activation of NLRP3 inflammasome. Furthermore, we found that AC treatment activated NAD(+)-dependent deacetylase Sirtuin 1 (SIRT1), resulting in reduced acetylation level of NLRP3. Molecular modeling analysis revealed that binding of AC to sirtuin-activating compound-binding domain increased the affinity of the substrate to the catalytic domain of SIRT1. Moreover, AC (80 mu M) significantly attenuated macrophage-conditioned medium-induced inflammatory responses in 3T3-L1 adipocytes. In LPS-induced acute inflammatory mice, administration of AC (20, 60 mg center dot kg(-1)center dot d(-1), ip) for 5 days significantly suppressed the pro-inflammatory cytokine levels in serum and epididymal white adipose tissue (eWAT), attenuated macrophage infiltration into eWAT, and mitigated adipose tissue inflammation. The beneficial effects of AC were blocked by co-administration of a selective SIRT1 inhibitor EX-527 (10 mg center dot kg(-1)center dot d(-1)). Taken together, AC suppresses NLRP3-mediated IL-1 beta secretion through activating SIRT1, leading to attenuated inflammation in macrophages and adipose tissue, which might be a candidate to treat obesity-associated metabolic diseases.
WOS关键词GENE-EXPRESSION ; CELL-SURVIVAL ; FATTY-ACID ; OBESITY ; ACTIVATION ; TARGET ; INTERLEUKIN-1-BETA ; ACETYLATION ; MACROPHAGES ; ADIPOCYTES
资助项目National Natural Science Foundation of China[81872754] ; Science and Technology Commission of Shanghai Municipality[20430780300] ; Science and Technology Commission of Shanghai Municipality[19431908100] ; Science and Technology Development Fund, Macao SAR, China[FDCT 0031/2019/A1] ; Research Fund of University of Macau[MYRG2018-00037-ICMS]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000719724100003
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/299003]  
专题新药研究国家重点实验室
通讯作者Ye, Yang; Lin, Li-gen
作者单位1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res & Nat Prod, Chem Dept, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Cheng,Ren, Yong-mei,Zhu, Jian-zhong,et al. Ainsliadimer C, a disesquiterpenoid isolated from Ainsliaea macrocephala, ameliorates inflammatory responses in adipose tissue via Sirtuin 1-NLRP3 inflammasome axis[J]. ACTA PHARMACOLOGICA SINICA,2021:13.
APA Chen, Cheng.,Ren, Yong-mei.,Zhu, Jian-zhong.,Chen, Jia-li.,Feng, Zhe-ling.,...&Lin, Li-gen.(2021).Ainsliadimer C, a disesquiterpenoid isolated from Ainsliaea macrocephala, ameliorates inflammatory responses in adipose tissue via Sirtuin 1-NLRP3 inflammasome axis.ACTA PHARMACOLOGICA SINICA,13.
MLA Chen, Cheng,et al."Ainsliadimer C, a disesquiterpenoid isolated from Ainsliaea macrocephala, ameliorates inflammatory responses in adipose tissue via Sirtuin 1-NLRP3 inflammasome axis".ACTA PHARMACOLOGICA SINICA (2021):13.

入库方式： OAI收割

来源：上海药物研究所

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。