School of Biology, Institute of Science, Suranaree University of Technology, Muang District, Nakhonratchasima, Thailand.
Phytomedicine. 2010 Dec 15;18(1):40-5. doi: 10.1016/j.phymed.2010.09.003. Epub 2010 Oct 30.
The purpose of this investigation was to extract and identify the bioactive phytochemicals from smaller galanga (Alpinia officinarum Hance). The antibacterial, synergy effects and primary mechanism of action of galangin and ceftazidime against S. aureus DMST 20651 are also investigated by minimum inhibitory concentration (MIC), checkerboard, killing curve determinations, enzyme assay and electronmicroscopy method. The rhizomes chloroform extract of this plant showed that these compounds were galangin, kaempferide and kaempferide-3-O-β-D-glucoside, which had not been previously reported in this species. Synergistic FIC indices were observed in the combination of test flavonoids (galangin, quercetin and baicalein) and all selected β-lactams (methicillin, ampicillin, amoxicillin, cloxacillin, penicillin G and ceftazidime) (FIC index, <0.02-0.11). The combination of ceftazidime at 5 μg/ml and 5 μg/ml of test flavonoids (galangin, quercetin and baicalein) exhibited synergistic effect by reduced the cfu/ml of this strain to 1×10(3) over 6 and throughout 24 h. Galangin showed marked inhibitory activity against penicillinase and β-lactamase. Electronmicroscopy clearly showed that the combination of galangin and ceftazidime caused damage to the ultrastructures of the cells of this strain. It was concluded that galangin, quercetin and baicalein exhibited the potential to reverse bacterial resistance to β-lactam antibiotics against penicillin-resistant S. aureus (PRSA). This may involve three mechanisms of action that galangin inhibit protein synthesis and effect on PBP 2a, interact with penicillinase and cause cytoplasmic membrane damage. These findings lead us to develop a new generation of phytopharmaceuticals that may use galangin, quercetin and baicalein in combination with ceftazidime to treat PRSA that currently almost untreatable microorganism. The anti-PRSA activity and mode of action of galangin is reported for the first time. These in vitro results have to be still confirmed in an animal test or in humans.
本研究旨在从小良姜（Alpinia officinarum Hance）中提取并鉴定具有生物活性的植物化学成分。还通过最低抑菌浓度（MIC）、棋盘试验、杀菌曲线测定、酶活性测定和电子显微镜方法，研究了高良姜素和头孢他啶对金黄色葡萄球菌 DMST 20651 的抗菌、协同作用和主要作用机制。该植物根茎的氯仿提取物表明，这些化合物为高良姜素、山柰酚和山柰酚-3-O-β-D-葡萄糖苷，此前在该种中尚未报道过。在所测试的黄酮类化合物（高良姜素、槲皮素和黄芩素）与所有选择的β-内酰胺类抗生素（苯唑西林、氨苄西林、阿莫西林、氯唑西林、青霉素 G 和头孢他啶）的组合中观察到协同 FIC 指数（FIC 指数，<0.02-0.11）。当头孢他啶浓度为 5μg/ml 与 5μg/ml 测试黄酮类化合物（高良姜素、槲皮素和黄芩素）组合时，该菌株的 cfuml 减少至 1×103，6 小时和 24 小时内协同作用明显。高良姜素对青霉素酶和β-内酰胺酶有明显的抑制活性。电子显微镜清楚地显示，高良姜素和头孢他啶的组合导致该菌株细胞的超微结构受损。结论是，高良姜素、槲皮素和黄芩素具有逆转耐青霉素金黄色葡萄球菌（PRSA）对β-内酰胺类抗生素耐药性的潜力。这可能涉及三种作用机制，即高良姜素抑制蛋白质合成和对 PBP2a 的作用、与青霉素酶相互作用和引起细胞质膜损伤。这些发现促使我们开发新一代植物药物，可能使用高良姜素、槲皮素和黄芩素与头孢他啶联合治疗目前几乎无法治疗的耐青霉素金黄色葡萄球菌。这是首次报道高良姜素抗 PRSA 的活性和作用方式。这些体外结果仍需在动物试验或人体中得到证实。
