Changchun University of Chinese Medicine.
Affiliated Hospital of Changchun University of Chinese Medicine.
Biol Pharm Bull. 2020;43(6):994-999. doi: 10.1248/bpb.b20-00034.
Streptococcus pneumoniae (S. pneumoniae) is an opportunistic pathogen that causes pneumonia, meningitis and bacteremia in humans and animals. Pneumolysin (PLY), a major pore-forming toxin that is important for S. pneumoniae pathogenicity, is a promising target for the development of anti-infective agents. Ephedra sinica granules (ESG) is one of the oldest medical preparation with multiple biological activities (such as a divergent wind and cold effect); however, the detailed mechanism remains unknown. In this study, we found that ESG treatment significantly inhibited the oligomerization of PLY and then reduced the activity of PLY without affecting S. pneumoniae growth and PLY production. In a PLY and A549 cell co-incubation system, the addition of ESG resulted in significant protection against PLY-mediated cell injury. Furthermore, S. pneumoniae-infected mice showed decreased mortality, and alleviated tissue damage and inflammatory reactions following treatment with ESG. Our results indicate that ESG is a potential candidate treatment for S. pneumoniae infection that targets PLY. This finding partially elucidates the mechanism of the Chinese herbal formula ESG in the treatment of pneumococcal disease.
肺炎链球菌(S. pneumoniae)是一种机会致病菌,可引起人类和动物的肺炎、脑膜炎和菌血症。肺炎球菌溶血素(PLY)是一种主要的孔形成毒素,对 S. pneumoniae 的致病性很重要,是开发抗感染药物的有前途的靶标。麻黄颗粒(ESG)是具有多种生物学活性(如发散风寒作用)的最古老的药物之一;然而,其详细机制尚不清楚。在这项研究中,我们发现 ESG 处理可显著抑制 PLY 的寡聚化,从而降低 PLY 的活性,而不影响肺炎链球菌的生长和 PLY 的产生。在 PLY 和 A549 细胞共孵育系统中,添加 ESG 可显著防止 PLY 介导的细胞损伤。此外,肺炎链球菌感染的小鼠在接受 ESG 治疗后,死亡率降低,组织损伤和炎症反应减轻。我们的结果表明,ESG 是一种针对 PLY 的治疗肺炎链球菌感染的潜在候选药物。这一发现部分阐明了中药配方 ESG 治疗肺炎球菌病的机制。