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来自卡普内烯:解读其与抗炎相关的化学特征。

Capnellenes from : Deciphering Their Anti-Inflammatory-Associated Chemical Features.

作者信息

Lai Kuei-Hung, Fan Yu-Chen, Peng Bo-Rong, Wen Zhi-Hong, Chung Hsu-Ming

机构信息

Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110301, Taiwan.

PhD Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 110301, Taiwan.

出版信息

Pharmaceuticals (Basel). 2023 Jun 22;16(7):916. doi: 10.3390/ph16070916.

Abstract

Through our ongoing research on investigating new anti-inflammatory terpenoids derived from soft corals, seven capnellenes sourced from were discovered. Among these, three were previously unknown compounds named Δ-capnellene-6α,8β-diol (), Δ-capnellene-6α,8β,10α-triol (), and Δ-capnellene-2β,8β,10α-triol (). The structures of all compounds were determined by spectroscopic analysis (IR, MS, 1D-, and 2D-NMR) and a comparison with the existing literature data. The compounds and were found to be the first-ever identified 6-hydroxy capnellenes. In the inflammation inhibitory assessments, compounds - were tested for their in vitro activities against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in LPS-induced RAW264.7 cells. Capnellenes and demonstrated significant reductions in iNOS levels (27.73% and 47.61%) at a concentration of 10 μM. Additionally, capnellenes , , and (at 10 μM) exhibited statistically significant inhibitions (ranging from 7.64% to 12.57%) against COX-2 protein expressions. Our findings indicated that the oxygen-bearing functionalities at C-8 and C-10 play critical roles in inhibiting iNOS protein induction, which can promote inflammation in LPS-induced RAW264.7 cells. Furthermore, a principal component analysis tool, the chemical global positioning system for natural products (ChemGPS-NP), was applied to confirm these capnellane-based sesquiterpenes as promising candidates for future anti-inflammatory agents targeting iNOS-related targets.

摘要

通过我们正在进行的关于从软珊瑚中提取新型抗炎萜类化合物的研究,发现了七种源自[具体来源未给出]的海松二烯类化合物。其中,有三种是以前未知的化合物,分别命名为Δ-海松二烯-6α,8β-二醇()、Δ-海松二烯-6α,8β,10α-三醇()和Δ-海松二烯-2β,8β,10α-三醇()。所有化合物的结构均通过光谱分析(红外光谱、质谱、一维和二维核磁共振)以及与现有文献数据进行比较来确定。化合物[具体化合物]和[具体化合物]被发现是首次鉴定出的6-羟基海松二烯类化合物。在炎症抑制评估中,对化合物[具体化合物] - [具体化合物]进行了体外抗脂多糖诱导的RAW264.7细胞中诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)蛋白表达活性的测试。海松二烯类化合物[具体化合物]和[具体化合物]在浓度为10μM时,iNOS水平显著降低(分别为27.73%和47.61%)。此外,海松二烯类化合物[具体化合物]、[具体化合物]和[具体化合物](在10μM时)对COX-2蛋白表达表现出统计学上显著的抑制作用(范围为7.64%至12.57%)。我们的研究结果表明,C-8和C-10位的含氧官能团在抑制iNOS蛋白诱导中起关键作用,iNOS蛋白诱导可促进脂多糖诱导的RAW264.7细胞中的炎症反应。此外,还应用了一种主成分分析工具——天然产物化学全球定位系统(ChemGPS-NP),以确认这些基于海松二烯的倍半萜类化合物是未来针对iNOS相关靶点的抗炎药物的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89c2/10383453/7de34b861f3c/pharmaceuticals-16-00916-g001.jpg

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