Ouyang Xiaojian, Li Xican, Liu Jie, Liu Yangping, Xie Yulu, Du Zhongcun, Xie Hong, Chen Ban, Lu Wenbiao, Chen Dongfeng
School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine Guangzhou 510006 China
School of Basic Medical Science, Guangzhou University of Chinese Medicine Guangzhou 510006 China
RSC Adv. 2020 Aug 21;10(52):31171-31179. doi: 10.1039/d0ra04896h.
Erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) were prepared and used to compare the ferroptosis inhibitory bioactivities of four monostilbenes, including rhapontigenin (1a), isorhapontigenin (1b), piceatannol-3'--glucoside (1c), and rhapontin (1d). Their relative levels were 1c ≈ 1b > 1a ≈ 1d in 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3,4-diaza--indacene-3-undecanoic acid (C11-BODIPY), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and flow cytometric assays. The comparison highlighted two 4'-OH-containing monostilbenes (1c and 1b) in ferroptosis inhibitory bioactivity. Similar structure-activity relationships were also observed in antioxidant assays, including 1,1-diphenyl-2-picryl-hydrazl radical (DPPH˙)-trapping, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO˙)-trapping, and Fe-reducing assays. UPLC-ESI-Q-TOF-MS analysis of the DPPH˙-trapping reaction of the monostilbenes revealed that they can inhibit ferroptosis in erastin-treated bmMSCs through a hydrogen donation-based antioxidant pathway. After hydrogen donation, these monostilbenes usually produce the corresponding stable dimers; additionally, the hydrogen donation potential was enhanced by the 4'-OH. The enhancement by 4'-OH can be attributed to the transannular resonance effect. This effect can be used to predict the inhibition potential of other π-π conjugative phenolics.
制备了经埃拉司亭处理的骨髓间充质干细胞（bmMSCs），并用于比较四种单芪类化合物（包括rhapontigenin（1a）、异rhapontigenin（1b）、piceatannol - 3'-葡萄糖苷（1c）和rhapontin（1d））的铁死亡抑制生物活性。在4,4 - 二氟 - 5 -（4 - 苯基 - 1,3 - 丁二烯基）- 4 - 硼 - 3,4 - 二氮杂 - 吲哚 - 3 - 十一烷酸（C11 - BODIPY）、3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基溴化四唑（MTT）和流式细胞术分析中，它们的相对水平为1c≈1b > 1a≈1d。该比较突出了两种含4'-OH的单芪类化合物（1c和1b）在铁死亡抑制生物活性方面的表现。在抗氧化分析中也观察到了类似的构效关系，包括1,1 - 二苯基 - 2 - 苦基肼自由基（DPPH˙）捕获、2 - 苯基 - 4,4,5,5 - 四甲基咪唑啉 - 1 - 氧基 - 3 - 氧化物自由基（PTIO˙）捕获和铁还原分析。对单芪类化合物DPPH˙捕获反应的超高效液相色谱 - 电喷雾 - 四极杆 - 飞行时间质谱（UPLC - ESI - Q - TOF - MS）分析表明，它们可通过基于氢供体的抗氧化途径抑制埃拉司亭处理的bmMSCs中的铁死亡。供氢后，这些单芪类化合物通常会产生相应的稳定二聚体；此外，4'-OH增强了氢供体潜力。4'-OH的增强作用可归因于跨环共振效应。该效应可用于预测其他π - π共轭酚类化合物的抑制潜力。
