College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China.
College of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine/College of Pharmacy/School Hospital, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing 210023, China.
Molecules. 2022 Oct 17;27(20):6952. doi: 10.3390/molecules27206952.
With the abuse of antibiotics, bacterial antibiotic resistance is becoming a major public healthcare issue. Natural plants, especially traditional Chinese herbal medicines, which have antibacterial activity, are important sources for discovering potential bacteriostatic agents. This study aimed to develop a fast and reliable method for screening out antimicrobial compounds targeting the MRSA membrane from Linn. seed. A UPLC-MS/MS method was applied to identify the prenylated flavonoids in major fractions from the extracts of Linn. seed. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of different fractions and compounds. The morphological and ultrastructural changes of MRSA were determined by scanning electron microscopy (SEM). The membrane-targeting mechanism of the active ingredients was explored by membrane integrity assays, membrane fluidity assays, membrane potential assays, ATP, and ROS determination. We identified eight prenylated flavonoids in Linn. seed. The antibacterial activity and mechanism studies showed that this type of compound has a unique destructive effect on MRSA cell membranes and does not result in drug resistance. The results revealed that prenylated flavonoids in Linn. seeds are promising candidates for the development of novel antibiotic agents to combat MRSA-associated infections.
随着抗生素的滥用，细菌的抗生素耐药性正成为一个主要的公共卫生健康问题。具有抗菌活性的天然植物，特别是传统中药，是发现潜在抑菌剂的重要来源。本研究旨在开发一种快速可靠的方法，从 Linn. 种子中筛选针对耐甲氧西林金黄色葡萄球菌（MRSA）膜的抗菌化合物。采用 UPLC-MS/MS 方法鉴定 Linn. 种子提取物中主要馏分中的类异戊二烯黄酮。采用肉汤微量稀释法测定不同馏分和化合物的最小抑菌浓度（MIC）。扫描电子显微镜（SEM）观察 MRSA 的形态和超微结构变化。通过膜完整性测定、膜流动性测定、膜电位测定、ATP 和 ROS 测定，探讨活性成分的膜靶向机制。我们从 Linn. 种子中鉴定出八种类异戊二烯黄酮。抗菌活性和机制研究表明，这类化合物对 MRSA 细胞膜具有独特的破坏作用，不会导致耐药性。研究结果表明 Linn. 种子中的类异戊二烯黄酮是开发新型抗生素药物对抗 MRSA 相关感染的有前途的候选药物。
