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穗花杉双黄酮通过靶向α-毒素和产气荚膜梭菌溶血素O减轻气性坏疽。

Amentoflavone Attenuates Gas Gangrene by Targeting Alpha-Toxin and Perfringolysin O.

作者信息

Liu Shui, Yang Xiaofeng, Zhang Hong, Zhang Jian, Zhou Yonglin, Wang Tingting, Hu Naiyu, Deng Xuming, Bai Xiaoxue, Wang Jianfeng

机构信息

Cadre's Ward, The First Hospital of Jilin University, Jilin University, Changchun, China.

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Institute of Zoonosis, Jilin University, Changchun, China.

出版信息

Front Pharmacol. 2020 Feb 28;11:179. doi: 10.3389/fphar.2020.00179. eCollection 2020.

Abstract

() type A strains are the main cause of gas gangrene in humans and animals. Treatment of this lethal disease is limited, and the prognosis is not good. Alpha-toxin (CPA) and perfringolysin O (PFO) secreted by play irreplaceable roles in cytotoxicity to host cells, persistence in host tissues, and lethality of gas gangrene pathology. This work determined the influence of amentoflavone, a biflavonoid isolated from and other plants, on hemolysis and cytotoxicity mediated by CPA and PFO and evaluated the therapeutic effect on gas gangrene. Our data showed that amentoflavone could block the hemolysis and cytotoxicity induced by CPA and PFO , thereby mediating significant protection against mortality of infected mice in a mouse gas gangrene model, efficient bacterial clearance in tissues and alleviation of histological damage . Based on the above results, amentoflavone may be a potential candidate against infection by reducing CPA and PFO-mediated virulence.

摘要

()A型菌株是人和动物气性坏疽的主要病因。这种致命疾病的治疗方法有限,预后不佳。由其分泌的α毒素(CPA)和产气荚膜梭菌溶血素O(PFO)在对宿主细胞的细胞毒性、在宿主组织中的持久性以及气性坏疽病理的致死性方面发挥着不可替代的作用。这项工作确定了从 及其他植物中分离出的双黄酮化合物穗花杉双黄酮对CPA和PFO介导的溶血和细胞毒性的影响,并评估了其对气性坏疽的治疗效果。我们的数据表明,穗花杉双黄酮可以阻断CPA和PFO诱导的溶血和细胞毒性,从而在小鼠气性坏疽模型中对感染小鼠的死亡率产生显著保护作用,实现组织中细菌的有效清除并减轻组织学损伤。基于上述结果,穗花杉双黄酮可能是一种通过降低CPA和PFO介导的毒力来对抗 感染的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f034/7059699/77e2a5ad57f5/fphar-11-00179-g001.jpg

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