Toxicology and Applied Pharmacology ( IF 3.3 ) Pub Date : 2018-12-07 , DOI: 10.1016/j.taap.2018.12.008 Zhuojian Sun , Qiu Li , Ranran Hou , Hongxiang Sun , Qihe Tang , Haixia Wang , Zhihui Hao , Songyao Kang , Tianli Xu , Shuang Wu
Klebsiella pneumoniae causes severe infections including pneumonia and sepsis and treatments are complicated by increased levels of antibiotic resistance. We have identified a flavonoid kaempferol-3-O-glucorhamnoside derived from the plant Thesium chinense Turcz that possessed potent anti-inflammatory effects in K. pneumoniae infected mice. Administration of kaempferol-3-O-glucorhamnoside before bacterial challenge effectively suppressed expression of the major inflammatory cytokines TNF-α, IL-6, IL-1β and PGE2 and ameliorated lung edema. In addition, administration of this compound to cultured RAW macrophages or Balb/c mice resulted in the suppression of NFκB and MAP kinase phosphorylation indicating an inhibitory effect on inflammation in vitro and in vivo. Kaempferol-3-O-glucorhamnoside also decreased ROS levels and overall oxidative stress in lungs and in cultured cells generated by K. pneumoniae exposure. Taken together, kaempferol-3-O-glucorhamnoside is a potent anti-inflammatory in vitro and in vivo and is a promising therapeutic agent for treating K. pneumoniae infections in the clinic.
中文翻译:
山奈黄素-3- ö -glucorhamnoside抑制炎症反应通过MAPK和NF-κB途径在体外和体内
肺炎克雷伯菌引起严重的感染,包括肺炎和败血症,并且抗生素耐药性水平的提高使治疗变得复杂。我们已经鉴定出源自植物Thesium chinense Turcz的类黄酮kaempferol-3- O - glucorhamnoside ,在肺炎克雷伯菌感染的小鼠中具有有效的抗炎作用。Kaempferol-3- O的管理细菌攻击前的β-葡糖鼠李糖苷可有效抑制主要炎症细胞因子TNF-α,IL-6,IL-1β和PGE2的表达,并改善肺水肿。此外,该化合物对培养的RAW巨噬细胞或Balb / c小鼠的给药导致NFκB的抑制和MAP激酶的磷酸化指示在炎症的抑制效果的体外和体内。Kaempferol-3- O - glucorhamnoside还降低了肺和肺炎克雷伯菌暴露产生的培养细胞中的ROS水平和总氧化应激。总之,山奈酚-3- Ö -glucorhamnoside是一种强效的抗炎体外和体内在临床上是治疗肺炎克雷伯菌感染的有前途的治疗剂。