Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, China.
College of Life and Health, Nanjing Polytechnic Institute, 625 Geguan Road, Nanjing, 210048, Jiangsu, China.
Microb Biotechnol. 2022 Sep;15(9):2401-2410. doi: 10.1111/1751-7915.14095. Epub 2022 Jun 21.
The natural flavonoids luteolin and luteoloside have anti-bacterial, anti-inflammatory, anti-oxidant, anti-tumour, hypolipidemic, cholesterol lowering and neuroprotective effects, but their poor water solubility limits their application in industrial production and the pharmaceutical industry. In this study, luteolin-7-O-β-(6″-O-succinyl)-d-glucoside, a new compound that was prepared by succinyl glycosylation of luteolin by the organic solvent tolerant bacterium Bacillus amyloliquefaciens FJ18 in an 8.0% DMSO (v/v) system, was obtained and identified. Its greater water solubility (2293 times that of luteolin and 12 232 times that of luteoloside) provides the solution to the application problems of luteolin and luteoloside. The conversion rate of luteolin (1.0 g l ) was almost 100% at 24 h, while the yield of luteolin-7-O-β-(6″-O-succinyl)-d-glucoside reached 76.2%. In experiments involving the oxygen glucose deprivation/reoxygenation injury model of mouse hippocampal neuron cells, the cell viability was significantly improved with luteolin-7-O-β-(6″-O-succinyl)-d-glucoside dosing, and the expressions of the anti-oxidant enzyme HO-1 in the nucleus increased, providing a neuroprotective effect for ischemic cerebral cells. The availability of biosynthetic luteolin-7-O-β-(6″-O-succinyl)-d-glucoside, which is expected to replace luteolin and luteoloside, would effectively expand the clinical application value of luteolin derivatives.
天然类黄酮木樨草素和芦丁苷具有抗菌、抗炎、抗氧化、抗肿瘤、降血脂、降胆固醇和神经保护作用，但它们的水溶性差限制了它们在工业生产和制药行业中的应用。本研究通过有机溶剂耐受菌解淀粉芽孢杆菌在 8.0% DMSO（v/v）系统中对木樨草素进行琥珀酰化糖基化反应，得到并鉴定了一种新化合物木樨草素-7-O-β-(6″-O-琥珀酰基)-d-葡萄糖苷。其具有更大的水溶性（是木樨草素的 2293 倍，芦丁苷的 12232 倍），为解决木樨草素和芦丁苷的应用问题提供了方案。在 24 h 内，1.0 g/L 木樨草素的转化率几乎达到 100%，而木樨草素-7-O-β-(6″-O-琥珀酰基)-d-葡萄糖苷的产率达到 76.2%。在涉及小鼠海马神经元细胞氧葡萄糖剥夺/再复氧损伤模型的实验中，木樨草素-7-O-β-(6″-O-琥珀酰基)-d-葡萄糖苷给药可显著提高细胞活力，核内抗氧化酶 HO-1 的表达增加，为缺血性脑细胞提供神经保护作用。生物合成的木樨草素-7-O-β-(6″-O-琥珀酰基)-d-葡萄糖苷的可用性有望替代木樨草素和芦丁苷，将有效扩大木樨草素衍生物的临床应用价值。
