Piseth Nhoek , Seokyoung Hwang , Jungmoo Huh , Pisey Pel , Chan-Woong Park , Piseth Khiev , Hyun Woo Kim , Minsoo Noh , Young-Won Chin
{"title":"长生果树枝中的丁内酯和萜类二萜及其对脂肪生成素分泌的影响","authors":"Piseth Nhoek , Seokyoung Hwang , Jungmoo Huh , Pisey Pel , Chan-Woong Park , Piseth Khiev , Hyun Woo Kim , Minsoo Noh , Young-Won Chin","doi":"10.1016/j.bioorg.2024.107890","DOIUrl":null,"url":null,"abstract":"<div><div>Three butanolides derivatives, grewiifolides A–C, and nine clerodane diterpenes, grewiifolins M-U, as well as a known sterol were isolated from the twigs of <em>Casearia grewiifolia</em>. The chemical structures and configurations of all isolates were established by various spectroscopic means and chemical derivatization. In a cell-based phenotypic assay using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs), grewiifolide B significantly promoted adiponectin-secretion with EC<sub>50</sub> value of 24.8 µM. In target identification studies, butanolide derivatives were selectively bound to PPARγ with <em>K<sub>i</sub></em> values of 4.65, 0.55, and 17.8 µM, respectively. Further functional analysis and molecular modeling revealed that grewiifolide B promotes adiponectin-secretion through PPARγ full agonism.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"Article 107890"},"PeriodicalIF":5.1000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Butanolides and clerodane diterpenes from the twigs of Casearia grewiifolia and their effects on adiponectin secretion\",\"authors\":\"Piseth Nhoek , Seokyoung Hwang , Jungmoo Huh , Pisey Pel , Chan-Woong Park , Piseth Khiev , Hyun Woo Kim , Minsoo Noh , Young-Won Chin\",\"doi\":\"10.1016/j.bioorg.2024.107890\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Three butanolides derivatives, grewiifolides A–C, and nine clerodane diterpenes, grewiifolins M-U, as well as a known sterol were isolated from the twigs of <em>Casearia grewiifolia</em>. The chemical structures and configurations of all isolates were established by various spectroscopic means and chemical derivatization. In a cell-based phenotypic assay using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs), grewiifolide B significantly promoted adiponectin-secretion with EC<sub>50</sub> value of 24.8 µM. In target identification studies, butanolide derivatives were selectively bound to PPARγ with <em>K<sub>i</sub></em> values of 4.65, 0.55, and 17.8 µM, respectively. Further functional analysis and molecular modeling revealed that grewiifolide B promotes adiponectin-secretion through PPARγ full agonism.</div></div>\",\"PeriodicalId\":257,\"journal\":{\"name\":\"Bioorganic Chemistry\",\"volume\":\"153 \",\"pages\":\"Article 107890\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0045206824007958\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0045206824007958","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
从长生果树枝中分离出了三种丁内酯衍生物--长生果内酯 A-C，九种萜类二萜--长生果内酯 M-U，以及一种已知的甾醇。通过各种光谱手段和化学衍生方法，确定了所有分离物的化学结构和构型。在以人骨髓间充质干细胞（hBM-MSCs）脂肪生成模型为基础的细胞表型试验中，growiifolide B 能显著促进脂肪直链肽的分泌，EC50 值为 24.8 µM。在靶标鉴定研究中，丁内酯衍生物选择性地与 PPARγ 结合，Ki 值分别为 4.65、0.55 和 17.8 µM。进一步的功能分析和分子建模显示，growiifolide B 可通过 PPARγ 的完全激动作用促进脂肪直链素的分泌。
Butanolides and clerodane diterpenes from the twigs of Casearia grewiifolia and their effects on adiponectin secretion
Three butanolides derivatives, grewiifolides A–C, and nine clerodane diterpenes, grewiifolins M-U, as well as a known sterol were isolated from the twigs of Casearia grewiifolia. The chemical structures and configurations of all isolates were established by various spectroscopic means and chemical derivatization. In a cell-based phenotypic assay using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs), grewiifolide B significantly promoted adiponectin-secretion with EC50 value of 24.8 µM. In target identification studies, butanolide derivatives were selectively bound to PPARγ with Ki values of 4.65, 0.55, and 17.8 µM, respectively. Further functional analysis and molecular modeling revealed that grewiifolide B promotes adiponectin-secretion through PPARγ full agonism.
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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
