Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, P. R. China.
Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515. P. R. China.
Clin Sci (Lond). 2020 Oct 16;134(19):2549-2563. doi: 10.1042/CS20200598.
Acute lung injury (ALI) is a life-threatening disease without effective pharmacotherapies, so far. Forsythia suspensa is frequently used in the treatment of lung infection in traditional Chinese medicine. In search for natural anti-inflammatory components, the activity and the underlying mechanism of Forsythoside A (FA) from Forsythia suspensa were explored. In the present paper, BALB/c mice and murine RAW 264.7 cells were stimulated by LPS to establish inflammation models. Data showed that FA inhibited the production of TNF-α and IL-6 and the activation of STAT3 in LPS-stimulated RAW 264.7 cells. Additionally, FA increased the expression level of microRNA-124 (miR-124). Furthermore, the inhibitory effect of FA on STAT3 was counteracted by the treatment of miR-124 inhibitor. Critically, FA ameliorated LPS-induced ALI pathological damage, the increase in lung water content and inflammatory cytokine, cells infiltration and activation of the STAT3 signaling pathway in BALB/c mice. Meanwhile, FA up-regulated the expression of miR-124 in lungs, while administration with miR-124 inhibitor attenuated the protective effects of FA. Our results indicated that FA alleviates LPS-induced inflammation through up-regulating miR-124 in vitro and in vivo. These findings indicate the potential of FA and miR-124 in the treatment of ALI.
急性肺损伤(ALI)是一种危及生命的疾病,目前尚无有效的药物治疗方法。连翘在中药治疗肺部感染中经常被使用。为了寻找天然抗炎成分,本文研究了连翘苷(FA)的活性及其作用机制。本文采用 LPS 刺激 BALB/c 小鼠和 RAW264.7 细胞建立炎症模型。结果表明,FA 可抑制 LPS 刺激的 RAW264.7 细胞中 TNF-α和 IL-6 的产生以及 STAT3 的激活。此外,FA 可增加 microRNA-124(miR-124)的表达水平。进一步研究发现,FA 对 STAT3 的抑制作用可被 miR-124 抑制剂逆转。重要的是,FA 可改善 LPS 诱导的 ALI 病理损伤,降低肺水含量和炎症细胞因子水平,减少细胞浸润和 STAT3 信号通路的激活。同时,FA 可上调 LPS 诱导的 ALI 肺组织中 miR-124 的表达,而 miR-124 抑制剂可减弱 FA 的保护作用。这些结果表明,FA 通过体内和体外上调 miR-124 缓解 LPS 诱导的炎症反应。这些发现提示 FA 和 miR-124 可能在 ALI 的治疗中有一定的应用潜力。