Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD, 4878, Australia.
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD, 4878, Australia.
Chem Biol Interact. 2022 Dec 1;368:110124. doi: 10.1016/j.cbi.2022.110124. Epub 2022 Aug 22.
Two new galloyl glucosides, galloyl-lawsoniaside A (4) and uromyrtoside (6), were isolated from the polar fraction of Uromyrtus metrosideros leaf extract along with another four previously identified phytochemicals (1, 2, 3, and 5). The structures of these six compounds were characterised using low and high-resolution mass spectrometry (L/HRMS) and 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. These compounds were not toxic to human peripheral blood mononuclear cells (PBMCs) at 10 μg/mL over 24 h, yet showed significant in vitro suppression of proinflammatory cytokines involved in the pathogenesis of inflammatory bowel disease (IBD). Specifically, the release of interferon γ (IFN-γ), interleukin (IL)-17A, and IL-8 from phorbol myristate acetate/ionomycin (P/I) and anti-CD3/anti-CD28-activated cells were significantly suppressed by compounds 4 and 5. Interestingly, no effect on tumour necrosis factor (TNF) release was observed. These results show that the newly characterised compound 4 has promising cytokine suppressive properties, which could be further investigated as a candidate for IBD treatment.
从 Uromyrtus metrosideros 叶提取物的极性部分分离到两种新的没食子酰基葡萄糖苷，即没食子酰基劳森苷 A（4）和尿苷（6），以及另外四种先前鉴定的植物化学物质（1、2、3 和 5）。使用低和高分辨质谱（L/HRMS）和一维和二维核磁共振（NMR）光谱对这六种化合物的结构进行了表征。这些化合物在 24 小时内以 10μg/mL 的浓度对人外周血单核细胞（PBMC）没有毒性，但在体外显著抑制了参与炎症性肠病（IBD）发病机制的促炎细胞因子。具体而言，化合物 4 和 5 显著抑制佛波醇肉豆蔻酸乙酸酯/离子霉素（P/I）和抗 CD3/抗 CD28 激活细胞中干扰素 γ（IFN-γ）、白细胞介素（IL）-17A 和 IL-8 的释放。有趣的是，观察到对肿瘤坏死因子（TNF）释放没有影响。这些结果表明，新鉴定的化合物 4 具有有希望的细胞因子抑制特性，可进一步作为 IBD 治疗的候选药物进行研究。
