C-Glycosylflavones and Their (E)-p-Coumaroyl Acylated Derivatives from Episperm of Fenugreek Microgreen as Xanthine Oxidase Inhibitors
C-Glycosylflavones and Their (E)-p-Coumaroyl Acylated Derivatives from Episperm of Fenugreek Microgreen as Xanthine Oxidase Inhibitors
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DOI：
10.1007/s43450-023-00447-x
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发表时间：
2023-09
期刊：
影响因子：
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通讯作者：
Mengru Guo;Shiwei Sun;Hui Wang;Yichen Yin;Zhizhou Li;Chaoyi Lv;Wen Wang
中科院分区：
文献类型：
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作者：
Mengru Guo;Shiwei Sun;Hui Wang;Yichen Yin;Zhizhou Li;Chaoyi Lv;Wen Wang
胡芦巴外种皮70%甲醇可溶性提取物的生物活性导向化学研究，从豆科植物中分离出四种（E）-对香豆酰化C-糖基黄酮和四种C-糖基黄酮。其中两个6-C-糖基黄酮类化合物为首次从胡卢巴属植物中分离得到，命名为异牡荆素2″-O-（E）-p-香豆酸酯和异orientin 2″-O-（E）-p-香豆酸酯。所有化合物对黄嘌呤氧化酶的抑制作用进行了评价。其中异牡荆素2″-O-（E）-p-coumarate和异orientin 2″-O-（E）-p-coumarate的抑制效果最好，IC 50值分别为36.08 ± 0.93和35.85 ± 0.64 μM。酶动力学研究表明，化合物异牡荆素2″-O-（E）-p-香豆酸酯和异Orientin 2″-O-（E）-p-香豆酸酯的抑制类型均为混合型抑制。分子对接结果表明，（E）-对香豆酰化的6-C-糖基黄酮位于钼原子附近的蝶呤辅因子口袋中，可能引起黄嘌呤氧化酶蛋白活性构象的变化，从而抑制尿酸的生成。这些结果启发了我们对胡芦巴外种皮的回收利用，并进一步研究了（E）-对香豆酰酰化6-C-糖基黄酮作为黄嘌呤氧化酶抑制剂的药用价值。
A bioactivity-oriented chemical investigation of the 70% MeOH-soluble extract from the episperm of fenugreek microgreen,Trigonella foenum-graecumL., Fabaceae, led to the isolation of four (E)-p-coumaroyl acylatedC-glycosylflavones and fourC-glycosylflavones. Among them, two 6-C-glycosylflavones bearing a (E)-p-coumaroyl moiety, named isovitexin 2″-O-(E)-p-coumarate and isoorientin 2″-O-(E)-p-coumarate, were isolated for the first time from theTrigonellagenus. All compounds’ inhibitory effects were evaluated against xanthine oxidase. Isovitexin 2″-O-(E)-p-coumarate and isoorientin 2″-O-(E)-p-coumarate showed the best inhibitory effect with IC50values of 36.08 ± 0.93 and 35.85 ± 0.64 μM, respectively. Furthermore, enzyme kinetics revealed that the inhibition types of compounds isovitexin 2″-O-(E)-p-coumarate and isoorientin 2″-O-(E)-p-coumarate were all mixed-type inhibition. Molecular docking revealed that (E)-p-coumaroyl acylated 6-C-glycosylflavones reside at the molybdopterin cofactor pocket near the molybdenum atom, which may have caused the changes of active conformation of xanthine oxidase protein, and thus inhibited the production of uric acid. All the results inspired us to recycle the episperm of fenugreek microgreen and further investigated the medicinal values of (E)-p-coumaroyl acylated 6-C-glycosylflavones as xanthine oxidase inhibitors.Graphical Abstract