期刊
JOURNAL OF NATURAL PRODUCTS
卷 85, 期 6, 页码 1474-1485出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.1c01141
关键词
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资金
- National Natural Science Foundation of China [81673460, 81973460, U19A2011, 82172723]
- Science and Technology Department of Sichuan Province [2021YFN0134, 2021ZYD0079]
- Chengdu University of Traditional Chinese Medicine [CZYJC1905, 2020XSGG016, 2020JCRC006, SKL2021-19, SKL2021-42]
- National Interdisciplinary Innovation Team of Traditional Chinese Medicine [ZYYCXTD-D-202209]
Transcriptome analysis identified hydroanthraquinones with anti-inflammatory effects, which were confirmed through in vitro and in vivo assays. Further experiments revealed that one of the compounds could suppress the NF-kappa B signaling pathway, leading to its anti-inflammatory activity.
Transcriptome analysis is shown to be an effective strategy to understand the potential function of natural products. Here, it is reported that 11 previously undescribed hydroanthraquinones [nigroquinones A-K (1-11)], along with eight known congeners, were isolated from Nigrospora sphaerica. Their structures were elucidated by interpreting spectroscopic and spectrometric data including high-resolution mass spectra and nuclear magnetic resonance. The absolute configurations of 1-11 were confirmed by electronic circular dichroism calculations. Transcriptome analysis revealed that 3 (isolated in the largest amount) might be anti-inflammatory. Assays based on LPS-induced RAW264.7 macrophages and zebrafish embryos confirmed that some of the isolated hydroanthraquinones attenuated the secretion of pro-inflammatory mediators in vitro and in vivo. Further Western blotting and immunofluorescence experiments indicated that 4 (which showed the most obvious nitric oxide inhibition) could suppress the expression of nuclear factor-kappa-B (NF-kappa B), phosphorylation of the inhibitor of NF-kappa B kinase and inhibit the transportation of NF-kappa B to the nucleus. Hence, the suppression of the NF-kappa B signaling pathway may be responsible for the anti-inflammatory effect. These results show that bioactivity evaluation on the basis of transcriptome analysis may be effective in the functional exploration of natural products.
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