Fazly Bazzaz B S, Iranshahi M, Naderinasab M, Hajian S, Sabeti Z, Masumi E
Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, I.R.Iran.
Res Pharm Sci. 2010 Jan;5(1):21-8.
Galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana, and conferol, another sesquiterpene coumarin from F. badrakema, were evaluated for their effects on the reversal of multi-drug resistance in clinical isolates of Staphylococcus aureus and Escherichia coli, respectively. Neither galbanic acid (up to 1000 μg/ml) nor conferol (up to 400 μg/ml) by itself shows any antibacterial activities against tested strains. The minimum inhibitory concentrations (MICs) of ciprofloxacin and tetracycline were determined using macrodilution technique in the presence and absence of sub-inhibitory concentrations of galbanic acid (31.25-1000 μg/ml) or conferol (50-400 μg/ml), however they caused no change in MICs of the antibiotics. Galbanic acid did not show any inhibitory effect on efflux phenomenon of E. coli. This can be related to the outer membrane of gram-negative bacteria which is impermeable to lipophilic compounds or another mechanism rather than efflux responsible for resistance in tested E. coli strains. An inhibitory effect of conferol on the efflux was compared with verapamil as a positive control. Because efflux is the only known mechanism of resistance to ethidium bromide (model efflux substrate) and verapamil reduced MIC of ethidium bromide, efflux mechanism can be considered as one of the resistance mechanisms in tested S. aureus strains. Conferol, however, did not enhance the antibiotic efficacy mediated by inhibiting efflux pumps in bacteria.
分别评估了来自新疆阿魏的倍半萜香豆素没药酸以及来自费尔干纳阿魏的另一种倍半萜香豆素紫花前胡醇对金黄色葡萄球菌和大肠杆菌临床分离株多药耐药逆转的影响。没药酸（高达1000μg/ml）和紫花前胡醇（高达400μg/ml）单独使用时对受试菌株均无抗菌活性。在有和没有亚抑菌浓度的没药酸（31.25 - 1000μg/ml）或紫花前胡醇（50 - 400μg/ml）存在的情况下，采用常量稀释技术测定环丙沙星和四环素的最低抑菌浓度（MIC），然而它们并未改变抗生素的MIC。没药酸对大肠杆菌的外排现象没有任何抑制作用。这可能与革兰氏阴性菌的外膜有关，其对亲脂性化合物不透性，或者是另一种机制而非外排在受试大肠杆菌菌株耐药中起作用。将紫花前胡醇对外排的抑制作用与作为阳性对照的维拉帕米进行比较。由于外排是对溴化乙锭（模型外排底物）耐药的唯一已知机制，且维拉帕米降低了溴化乙锭的MIC，因此外排机制可被视为受试金黄色葡萄球菌菌株的耐药机制之一。然而，紫花前胡醇并未通过抑制细菌中的外排泵来增强抗生素疗效。
