Program for Natural Product Chemical Biology, Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
Program for Natural Product Chemical Biology, Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People's Republic of China.
J Ethnopharmacol. 2019 Jan 10;228:50-57. doi: 10.1016/j.jep.2018.09.011. Epub 2018 Sep 7.
The leaves of Rhodomyrtus tomentosa are traditionally used in the treatment of infectious diseases such as wound infections in Chinese traditional medicine. The mechanisms of the activity of rhodomyrtosone B (RDSB), a natural acylphloroglucinol isolated from the leaves of Rhodomyrtus tomentosa, are still not understood. We provided a detailed investigation of the antibacterial action of RDSB against bacteria in vitro and in vivo.
The antibacterial activity of RDSB was tested by the microdilution method against a panel of bacteria, and a time-killing assay was carried out according to CLSI guidelines. The cytotoxic potential of RDSB was evaluated against mammalian cells, and its haemolytic activity towards rabbit red blood cells (RBCs) was assessed. The mode of action of RDSB was investigated by targeting bacterial membranes, and its resistance was evaluated using a sequential passaging method. The antibacterial activities in vivo were assessed against MRSA in a mouse skin infection mode.
RDSB exhibited distinct antibacterial activities against selected Gram-positive pathogens responsible for serious infections, even including methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 0.62-1.25 µg/mL and vancomycin-resistant Enterococcus faecium (VRE) with an MIC of 2.5 µg/mL. RDSB displayed much more rapid bactericidal activity against MRSA than that of vancomycin. The membrane-targeting experiments revealed that RDSB exhibited significant antibacterial activity with the perturbation of bacterial membrane potential and an increase in membrane permeability. In particular, RDSB had weak cytotoxicity to mammalian cells (IC >14 µg/mL) and has advantageous specificity against selected Gram-positive bacterial membranes rather than RBCs. Notably, RDSB displayed in vitro antibacterial activities against MRSA without drug-resistance and profoundly attenuated the skin ulcer formation in a murine model of MRSA infection under a single dose of 40 µg RDSB per mouse.
RDSB has profound antibacterial activity against drug-resistant bacteria (MRSA and VRE) and low cytotoxicity. It is bactericidal in nature, and an increase in membrane permeability resulting from membrane perturbation is one of its modes of action. RDSB represents a promising natural antibiotic to combat drug-resistant (MRSA and VRE) infections.
桃金娘科的叶子在传统中药中用于治疗感染性疾病，如伤口感染。罗地莫尔酮 B（RDSB）是从桃金娘科叶子中分离出来的一种天然酰基间苯三酚，其活性机制尚不清楚。我们对 RDSB 对细菌的体外和体内抗菌作用进行了详细的研究。
采用微量稀释法测定 RDSB 对一系列细菌的抗菌活性，并按 CLSI 指南进行杀菌试验。评估 RDSB 对哺乳动物细胞的细胞毒性潜力，并评估其对兔红细胞（RBC）的溶血活性。通过靶向细菌膜来研究 RDSB 的作用方式，并通过连续传代法评估其耐药性。采用小鼠皮肤感染模型评估其体内对 MRSA 的抗菌活性。
RDSB 对引起严重感染的选定革兰氏阳性病原体具有明显的抗菌活性，甚至包括最小抑菌浓度（MIC）为 0.62-1.25μg/mL 的耐甲氧西林金黄色葡萄球菌（MRSA）和 MIC 为 2.5μg/mL 的万古霉素耐药粪肠球菌（VRE）。与万古霉素相比，RDSB 对 MRSA 的杀菌作用更快。膜靶向实验表明，RDSB 通过扰乱细菌膜电位和增加膜通透性表现出显著的抗菌活性。特别是，RDSB 对哺乳动物细胞的细胞毒性较弱（IC >14μg/mL），对选定的革兰氏阳性细菌膜具有优势特异性，而不是对 RBC 的特异性。值得注意的是，RDSB 在体外对 MRSA 具有抗菌活性而无耐药性，并且在每只小鼠 40μg RDSB 的单剂量下，可显著减轻 MRSA 感染小鼠模型中的皮肤溃疡形成。
RDSB 对耐药菌（MRSA 和 VRE）具有较强的抗菌活性和较低的细胞毒性。它具有杀菌作用，膜通透性的增加是其作用机制之一。RDSB 是一种有前途的天然抗生素，可用于治疗耐药（MRSA 和 VRE）感染。
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