Guo Tingting, Liu Peng, Wang Zeyu, Zheng Yuling, Huang Wenhua, Kong Decong, Ding Lizhong, Lv Qingyu, Wang Zhongtian, Jiang Hua, Jiang Yongqiang, Sun Liping
College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China.
Front Pharmacol. 2022 Jul 7;13:942180. doi: 10.3389/fphar.2022.942180. eCollection 2022.
Group A (GAS, ) is a common pathogen that can cause a variety of human diseases. Streptolysin O (SLO) is an exotoxin produced by GAS. It is a pore-forming toxin (PFT) that exhibits high toxicity. SLO enables GAS to evade phagocytosis and clearance by neutrophils, induces eukaryotic cell lysis, and activates inflammatory bodies. Luteolin is a natural compound that is produced by a wide range of plant species, and recent studies have shown that luteolin can inhibit the growth and alter the morphological of GAS. Here, we reported that luteolin can weaken the cytotoxicity and hemolytic activity of SLO . Briefly, luteolin bound SLO with high affinity, inhibited its dissolution of erythrocytes, affected its conformational stability and inhibited the formation of oligomers. To further verify the protective effect of luteolin, we used an SLO-induced human laryngeal carcinoma epithelial type-2 cells (HEp-2) model. Notably, our results showed luteolin protected HEp-2 cells from SLO induced cytotoxicity and changed in cell membrane permeability. In addition, we explored the role of luteolin in protecting mice from GAS-mediated injury using an aerosolized lung delivery model, and our results indicate that luteolin increases murine survival rate following inoculation with a lethal dose of GAS, and that survival was also associated with decreased pathological damage to lung tissue. Our results suggest that luteolin may be a novel drug candidate for the treatment of GAS infection.
A组（A群链球菌，GAS）是一种常见病原体，可导致多种人类疾病。链球菌溶血素O（SLO）是A群链球菌产生的一种外毒素。它是一种孔形成毒素（PFT），具有高毒性。SLO使A群链球菌能够逃避中性粒细胞的吞噬和清除，诱导真核细胞裂解，并激活炎性小体。木犀草素是一种由多种植物物种产生的天然化合物，最近的研究表明，木犀草素可以抑制A群链球菌的生长并改变其形态。在此，我们报道木犀草素可以减弱SLO的细胞毒性和溶血活性。简而言之，木犀草素以高亲和力结合SLO，抑制其对红细胞的溶解，影响其构象稳定性并抑制寡聚体的形成。为了进一步验证木犀草素的保护作用，我们使用了SLO诱导的人喉癌上皮2型细胞（HEp-2）模型。值得注意的是，我们的结果表明木犀草素可保护HEp-2细胞免受SLO诱导的细胞毒性和细胞膜通透性变化的影响。此外，我们使用雾化肺部给药模型探索了木犀草素在保护小鼠免受A群链球菌介导的损伤中的作用，我们的结果表明，木犀草素可提高接种致死剂量A群链球菌后小鼠的存活率，并且存活率还与肺组织病理损伤的减少有关。我们的结果表明，木犀草素可能是治疗A群链球菌感染的新型候选药物。
