Identification of Ecdysteroid Sinapate Esters with COX-2 Inhibitory Effects from Fibraurea recisa Using Molecular Networking and MS2LDA,Journal of Natural Products

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Identification of Ecdysteroid Sinapate Esters with COX-2 Inhibitory Effects from Fibraurea recisa Using Molecular Networking and MS2LDA
Journal of Natural Products ( IF 3.3 ) Pub Date : 2023-08-02 , DOI: 10.1021/acs.jnatprod.3c00371
Yuya Kakumu , Minh Tu Thi Nguyen _{1,

2} , Tohru Mitsunaga , Hiroyuki Hattori ₃

Affiliation

The roots of Fibraurea recisa are recognized as a rich source of protoberberine and aporphine alkaloids, but the non-alkaloidal metabolites in this plant are underexplored. The present study investigated the chemical composition of the plant roots using untargeted metabolomics-based molecular networking and MS2LDA motif annotation, revealing the presence of a characteristic fragment motif related to several sinapoyl-functionalized metabolites. Guided by the targeted motif, two new sinapic acid–ecdysteroid hybrids, named 3-O-sinapoyl makisterone A (1) and 2-O-sinapoyl makisterone A (2), were isolated. The structures of these compounds, including their absolute configuration, were elucidated by HR-ESIQTOFMS, MS² fragmentation, NMR spectroscopy, and chemical degradation coupled with optical rotation measurements. Although neither compound inhibited nitric oxide (NO) production or inducible nitric oxide synthase (iNOS) protein expression on lipopolysaccharide-induced RAW 264 cells, 2 significantly suppressed cyclooxygenase 2 (COX-2) protein expression at 1–30 μM. Additionally, decreased expression of COX-2 protein was barely observed after treatment with methyl sinapate or makisterone A, the steroid skeleton of 1 and 2. These results indicated that the presence of the sinapoyl moiety at C-2 on the C₂₈-ecdysteroid skeleton played a key role in the selectivity for the suppression of the COX-2 protein expression.

中文翻译：

使用分子网络和 MS2LDA 鉴定来自 Fibraurea reisa 的具有 COX-2 抑制作用的蜕皮激素芥子酸酯

Fibraurea recisa的根被认为是原小檗碱和阿朴啡生物碱的丰富来源，但该植物中的非生物碱代谢物尚未得到充分研究。本研究使用基于非靶向代谢组学的分子网络和 MS2LDA 基序注释研究了植物根的化学成分，揭示了与几种芥子酰功能化代谢物相关的特征片段基序的存在。在目标基序的指导下，分离出两种新的芥子酸-蜕皮甾酮杂合体，命名为 3- O-芥子酰马基甾酮 A ( 1 ) 和 2- O-芥子酰马基甾酮 A ( 2 )。^{这些化合物的结构，包括它们的绝对构型，通过HR-ESIQTOFMS、MS 2}碎裂、NMR 光谱以及化学降解和旋光测量来阐明。虽然这两种化合物都不会抑制脂多糖诱导的 RAW 264 细胞上一氧化氮 (NO) 的产生或诱导型一氧化氮合酶 (iNOS) 蛋白的表达，但 2 在 1–30 μM浓度下显着抑制环氧合酶 2 (COX-2) 蛋白的表达。此外，用芥子酸甲酯或马克甾酮A（ 1和2的类固醇骨架）处理后，几乎没有观察到COX-2 蛋白表达的降低。_{这些结果表明C 28} -蜕皮甾类骨架上C-2处芥子酰基部分的存在在选择性抑制COX-2蛋白表达中发挥关键作用。

更新日期：2023-08-02

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