School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China; School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China; The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosafety, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Bioorg Chem. 2022 Jul;124:105826. doi: 10.1016/j.bioorg.2022.105826. Epub 2022 Apr 25.
Thirty-two undescribed coumarin-monoterpenes, including the first report of six pairs of enantiomeric and twenty congeners, were isolated from the petroleum ether extract of the stems of Gerbera anandria (Linn.) Sch.-Bip. Structurally, these compounds represented C3-substituted 5-methyl-4-hydroxycoumarin-monoterpenes. Among them, 1-7 and 10-24 were rare 5-methylcoumarin-monoterpenes formed through a furan ring. Their chemical structures and absolute configurations were determined by comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR spectroscopic data, Mosher's method, ECD calculations and single crystal X-ray diffraction. Furthermore, biological studies revealed that compounds 1-3, 3a, 5, 5a, 11-12, 21-22 and 26 had the neuroprotective effects on scopolamine-induced injury in PC12 cells. Notably, 3 exhibited the strongest neuroprotective activity with the cell viability values of 77.24%. Meanwhile, pretreatment with 3 significantly downregulate apoptosis and reactive oxygen species (ROS) production, as well as strengthen antioxidant enzyme activities (MDA and SOD). Moreover, pretreatment with 3 also could attenuate the down-regulation of HO-1 and Nrf2 induced by scopolamine. In conclusion, these results demonstrated that these compounds possessed the protective effects on scopolamine-injured PC12 cells through anti-apoptotic and anti-oxidant activities.
从非洲雏菊（Gerbera anandria（Linn.）Sch.-Bip.）茎的石油醚提取物中分离得到了 32 种未被描述的香豆素-单萜类化合物，包括首次报道的 6 对对映异构体和 20 种同系物。从结构上讲，这些化合物代表 C3-取代的 5-甲基-4-羟基香豆素-单萜类化合物。其中，1-7 和 10-24 是罕见的通过呋喃环形成的 5-甲基香豆素-单萜类化合物。通过综合分析包括高分辨质谱（HRESIMS）、1D 和 2D NMR 光谱数据、Mosher 法、ECD 计算和单晶 X 射线衍射在内的光谱数据，确定了它们的化学结构和绝对构型。此外，生物研究表明，化合物 1-3、3a、5、5a、11-12、21-22 和 26 对东莨菪碱诱导的 PC12 细胞损伤具有神经保护作用。值得注意的是，化合物 3 表现出最强的神经保护活性，细胞活力值为 77.24%。同时，3 预处理可显著下调凋亡和活性氧（ROS）的产生，并增强抗氧化酶的活性（MDA 和 SOD）。此外，3 预处理还可以减轻东莨菪碱诱导的 HO-1 和 Nrf2 的下调。综上所述，这些结果表明，这些化合物通过抗凋亡和抗氧化活性对东莨菪碱损伤的 PC12 细胞具有保护作用。
