{"title":"Structurally diverse meroterpenoids from Arnebia euchroma and their anti-inflammatory effects through NF-κB pathway.","authors":"Xiaojing Shi, Shengyun Dai, Jianguo Song, Shuyuan Zhang, Wenhao Zhang, Yao Guo, Shujing Zhang, Ying Wang, Wencai Ye, Jian Zheng, Xiaochi Ma, Wenyu Zhao","doi":"10.1016/j.bioorg.2024.108048","DOIUrl":null,"url":null,"abstract":"<p><p>Meroterpenoids in the traditional Chinese medicine Arnebia euchroma are thought to be key components in its anti-inflammatory activity. In the present study, 17 meroterpenoids including four types of structural skeletons (1-17), together with a monoterpenoid (18), were isolated from the roots of A. euchroma. HRESIMS, 1D and 2D NMR, electronic circular dichroism, and quantum computing-assisted methods were employed to determine the structures of four previously undescribed compounds (1-3, and 14). Zicaomeroterin B (2) feature with a novel benzo[b]oxepin moiety was confirmed by X-ray analysis based on the crystalline mate method. Meroterpenoids 2, 5, 6, 13, and 17 exhibited significant inhibition against the production of NO, IL-6, and TNF-α in LPS-stimulated macrophages without obvious cytotoxic effects. Furthermore, compounds 2, 5, and 6 significantly inhibited the phosphorylation activation of NF-κB p65 and its nuclear translocation in luciferase reporter test, immunoblotting, and immunofluorescence imaging, which in turn inhibited the NF-κB pathway and exerted anti-inflammatory effects. These findings suggested that meroterpenoids 2, 5, and 6 in A. euchroma are the potential lead compounds for anti-inflammatory agents based on NF-κB signaling pathway.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"154 ","pages":"108048"},"PeriodicalIF":4.5000,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.bioorg.2024.108048","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Meroterpenoids in the traditional Chinese medicine Arnebia euchroma are thought to be key components in its anti-inflammatory activity. In the present study, 17 meroterpenoids including four types of structural skeletons (1-17), together with a monoterpenoid (18), were isolated from the roots of A. euchroma. HRESIMS, 1D and 2D NMR, electronic circular dichroism, and quantum computing-assisted methods were employed to determine the structures of four previously undescribed compounds (1-3, and 14). Zicaomeroterin B (2) feature with a novel benzo[b]oxepin moiety was confirmed by X-ray analysis based on the crystalline mate method. Meroterpenoids 2, 5, 6, 13, and 17 exhibited significant inhibition against the production of NO, IL-6, and TNF-α in LPS-stimulated macrophages without obvious cytotoxic effects. Furthermore, compounds 2, 5, and 6 significantly inhibited the phosphorylation activation of NF-κB p65 and its nuclear translocation in luciferase reporter test, immunoblotting, and immunofluorescence imaging, which in turn inhibited the NF-κB pathway and exerted anti-inflammatory effects. These findings suggested that meroterpenoids 2, 5, and 6 in A. euchroma are the potential lead compounds for anti-inflammatory agents based on NF-κB signaling pathway.
期刊介绍:
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.