背景:肺炎是病原体感染后死亡的主要原因之一。干姜(GANJIANG)是一种与其他中药结合使用的草药,用于治疗病原体,例如病毒引起的肺炎。然而,六氢姜黄素(HHC)的影响,一种来自干姜的成分,肺炎仍然未知。
目的:本研究旨在探讨HHC对脂多糖(LPS)诱导的急性肺炎的影响。并阐明其潜在机制。
方法:气管内注射LPS建立C57BL/6小鼠肺炎模型,评价HHC对体内肺损伤和炎症的治疗作用。RAW264.7巨噬细胞用于说明体外HHC的细胞机制。
结果:HHC减轻了肺损伤,肺炎小鼠体内ROS和炎性细胞因子IL-6的产生。分子对接结果揭示了HHC与JAK1蛋白的结合。研究进一步表明,HHC抑制炎症细胞因子,如IL-6,TNF-α,IL-1β基因表达,抑制JAK1而不是JAK3的磷酸化,以及随后在LPS激活的巨噬细胞中STAT3的磷酸化。HHC在体外对JAK1和STAT3的蛋白质水平无影响。始终如一,HHC还在体内减弱了肺炎小鼠中的JAK1、STAT3磷酸化。
结论:结果显示HHC通过靶向抑制JAK1/STAT3信号通路减轻肺炎。它表明了HHC治疗肺炎的新作用,及其在JAK抑制剂治疗疾病中的潜在应用。
BACKGROUND: Pneumonia is one of the major causes of death after pathogens infection. Zingiberis rhizoma (GAN JIANG) is a herb that used in combination with other Chinese medicines to treat pathogen such as virus induced pneumonia. However, the affect of hexahydrocurcumin (HHC), a component from Zingiberis rhizoma, on pneumonia remains unknown.
OBJECTIVE: This study aims to explore the effects of HHC on lipopolysaccharide (LPS)-induced acute pneumonia, and to clarify the underlying mechanism.
METHODS: The pneumonia model of C57BL/6 mice was established by intratracheal injection of LPS to evaluate the therapeutic effect of HHC on lung injury and inflammation in vivo. RAW264.7 macrophages were utilized to illustrate the cellular mechanism of HHC in vitro.
RESULTS: HHC alleviated lung injury, ROS and inflammatory cytokine IL-6 production in pneumonia mice in vivo. Molecular docking results disclosed the binding of HHC to
JAK1 protein. The study further showed that HHC suppressed the inflammatory cytokines such as IL-6, TNF-α, IL-1β gene expression, inhibited the phosphorylation of
JAK1 but not JAK3, and the subsequent STAT3 phosphorylation in LPS-activated macrophages. HHC exhibited no effects on the protein levels of
JAK1 and STAT3 in vitro. Consistently, HHC also attenuated the
JAK1, STAT3 phosphorylation in pneumonia mice in vivo.
CONCLUSIONS: The results reveal that HHC attenuates pneumonia by targeted inhibition of
JAK1/STAT3 signaling pathway. It indicates the novel role of HHC to treat pneumonia, and its potential applications for JAK inhibitor-treated diseases.