Hydroanthraquinones from Nigrospora sphaerica and Their Anti-inflammatory Activity Uncovered by Transcriptome Analysis
Hydroanthraquinones from Nigrospora sphaerica and Their Anti-inflammatory Activity Uncovered by Transcriptome Analysis
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DOI：
10.1021/acs.jnatprod.1c01141
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发表时间：
2022-06-24
影响因子：
5.1
通讯作者：
Guo, Da-Le
中科院分区：
文献类型：
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作者：
Kuang, Qi-Xuan;Luo, Yan;Guo, Da-Le
转录组分析被证明是了解天然产物潜在功能的有效策略。本文报道了从球形黑孢菌（Nigrospora sphaerica）中分离出11种以前未描述的氢化蒽醌[苯胺醌A-K（1-11）]，沿着8种已知的同类物。通过解释光谱和光谱数据（包括高分辨率质谱和核磁共振）来阐明它们的结构。通过电子圆二色性计算证实了1-11的绝对构型。转录组分析显示，3（分离量最大）可能是抗炎的。基于LPS诱导的RAW 264.7巨噬细胞和斑马鱼胚胎的测定证实，一些分离的氢化蒽醌在体外和体内减弱促炎介质的分泌。进一步的Western blotting和免疫荧光实验表明，对NO抑制作用最明显的化合物4能够抑制核因子-κ B（NF-κ B B）的表达，抑制NF-κ B B激酶抑制剂的磷酸化，抑制NF-κ B B向细胞核的转运。因此，NF-κ B信号通路的抑制可能是抗炎作用的原因。这些结果表明，基于转录组分析的生物活性评价可能是有效的天然产物的功能探索。
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.