Department of Respiratory Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
Sci Rep. 2024 May 6;14(1):10361. doi: 10.1038/s41598-024-60646-x.
Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.
慢性阻塞性肺疾病(COPD)是一种以慢性气道炎症为特征的进行性疾病。一种日本草药,厚朴七物汤(TJ-41),在日本被广泛用于治疗慢性炎症性疾病。本研究旨在分析 TJ-41 在体内的抗炎作用及其潜在机制。我们通过气管内给予猪胰弹性蛋白酶和脂多糖(LPS)建立了 COPD 小鼠模型,并分析了 TJ-41 给药前后的情况。TJ-41 饮食在急性和慢性阶段减少了肺部炎症细胞浸润和急性阶段的体重减轻。体外实验表明,TJ-41 处理抑制了 BEAS-2B 细胞中 LPS 诱导的炎症细胞因子。此外,TJ-41 给药在细胞和小鼠实验中均激活了 AMP 激活的蛋白激酶(AMPK)通路,并抑制了雷帕霉素的机制靶点(mTOR)通路。我们得出结论,TJ-41 给药减轻了 COPD 小鼠模型中的气道炎症,这可能是通过激活的 AMPK 通路调节的,并抑制了 mTOR 通路。