School of Pharmacy, Fudan University, Shanghai, 201203, China.
Phytother Res. 2014 Jul;28(7):1071-6. doi: 10.1002/ptr.5098. Epub 2013 Dec 12.
Synergy is now a widely recognized approach that has direct applicability for new pharmaceuticals. The ethanolic extract of the aerial parts of the herb Sophora moorcroftiana showed significant antibacterial activity against drug-resistant Staphylococcus aureus, and its minimum inhibitory concentration (MIC) was 8 µg/mL. In a phytochemical study of the extract, five flavonoids were obtained. However, the isolates exhibited antibacterial activity in the range of 32-128 µg/mL, which was weaker than the extract. In combination with antibiotics, the antibacterially inactive compound genistein (1) and diosmetin (4) showed significant synergistic activity against drug-resistant S. aureus. In combination with norfloxacin, genistein (1) reduced the MIC to 16 µg/mL and showed synergy against strain SA1199B with a fractional inhibitory concentration index (FICI) of 0.38. With the antibiotics norfloxacin, streptomycin and ciprofloxacin, diosmetin (4) showed synergy against SA1199B, RN4220 and EMRSA-15, with FICI values of 0.38, 0.38 and 0.09, respectively. In an efflux experiment to elucidate a plausible mechanism for the observed synergy, genistein showed marginal inhibition of the NorA efflux protein.
协同作用是一种广泛认可的方法,它对新药物具有直接的适用性。该草药地上部分的乙醇提取物对耐药性金黄色葡萄球菌具有显著的抗菌活性,其最小抑菌浓度(MIC)为 8μg/mL。在对提取物的植物化学研究中,获得了五种类黄酮。然而,分离物的抗菌活性范围在 32-128μg/mL 之间,弱于提取物。与抗生素联合使用时,抗菌无效的化合物染料木黄酮(1)和二氢芹菜素(4)对耐药性金黄色葡萄球菌表现出显著的协同作用。与诺氟沙星联合使用时,染料木黄酮(1)将 MIC 降低至 16μg/mL,并对 SA1199B 菌株表现出协同作用,其部分抑菌浓度指数(FICI)为 0.38。与抗生素诺氟沙星、链霉素和环丙沙星联合使用时,二氢芹菜素(4)对 SA1199B、RN4220 和 EMRSA-15 表现出协同作用,FICI 值分别为 0.38、0.38 和 0.09。在阐明观察到的协同作用的可能机制的外排实验中,染料木黄酮对 NorA 外排蛋白显示出轻微的抑制作用。