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

TITLE=Amentoflavone Attenuates Clostridium perfringens Gas Gangrene by Targeting Alpha-Toxin and Perfringolysin O

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00179

DOI=10.3389/fphar.2020.00179

ISSN=1663-9812

ABSTRACT=<p><italic>Clostridium perfringens</italic> (<italic>C. perfringens</italic>) 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 <italic>C. perfringens</italic> 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 <italic>Selaginella tamariscina</italic> and other plants, on hemolysis and cytotoxicity mediated by CPA and PFO and evaluated the <italic>in vivo</italic> therapeutic effect on gas gangrene. Our data showed that amentoflavone could block the hemolysis and cytotoxicity induced by CPA and PFO <italic>in vitro</italic>, 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 <italic>in vivo</italic>. Based on the above results, amentoflavone may be a potential candidate against <italic>C. perfringens</italic> infection by reducing CPA and PFO-mediated virulence.</p>