Zhao Xiaoran, Liu Bowen, Liu Shui, Wang Lin, Wang Jianfeng
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University.
Biol Pharm Bull. 2017;40(1):61-67. doi: 10.1248/bpb.b16-00598.
Pneumolysin (PLY) is a devastating bacterial protein toxin of Streptococcus pneumoniae that punctures the cytomembrane, leading to pathological reactions, such as cell disruption and inflammation. Drugs capable of closely impacting the toxin are considered advantageous in the treatment of bacterial infections. Amentoflavone (AMF) is a chemical substance extracted from traditional Chinese herbs. Previous studies have demonstrated that AMF has multiple pharmacological effects and mentioned without attenuating pneumolysin-mediated cytotoxicity. This work focuses on the influence of AMF on inhibitory hemolytic mechanisms. AMF interacts with the toxin at Ser254, Glu277, Arg359, and effectively weakens the oligomerization of wild-type PLY and provides considerable protection against pneumolysin-mediated human alveolar epithelial (A549) cell damage. The results of our study demonstrate that AMF could be a candidate against pneumolysin-related injury.
肺炎溶血素（PLY）是肺炎链球菌产生的一种具有破坏性的细菌蛋白毒素，它能穿透细胞膜，引发细胞破裂和炎症等病理反应。能够紧密作用于该毒素的药物被认为在治疗细菌感染方面具有优势。穗花杉双黄酮（AMF）是一种从传统中草药中提取的化学物质。先前的研究表明，AMF具有多种药理作用，且未提及会减弱肺炎溶血素介导的细胞毒性。这项工作聚焦于AMF对抑制溶血机制的影响。AMF与毒素在Ser254、Glu277、Arg359位点相互作用，有效减弱野生型PLY的寡聚化，并为肺炎溶血素介导的人肺泡上皮（A549）细胞损伤提供显著保护。我们的研究结果表明，AMF可能是一种对抗肺炎溶血素相关损伤的候选药物。
