The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema

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  • Isago Hideaki
    Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo Hospital Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Mitani Akihisa
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Kohno Shiho
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Nagoshi Saki
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Ishimori Taro
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Saito Minako
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Tamiya Hiroyuki
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Miyashita Naoya
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Ishii Takashi
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Matsuzaki Hirotaka
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Yatomi Yutaka
    Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo Hospital
  • Nagase Takahide
    Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo
  • Jo Taisuke
    Department of Health Services Research, Graduate School of Medicine, the University of Tokyo

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Abstract

<p>Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder. It often causes weight loss, which is considered a poor prognostic factor. A Japanese herbal Kampo medicine, Hochuekkito (TJ-41), has been reported to prevent systemic inflammation and weight loss in COPD patients, but the underlying biological mechanisms remain unknown. In the present study, we investigated the role of TJ-41 in vivo using a mouse model of lung emphysema. We used lung epithelium-specific Taz conditional knockout mice (Taz CKO mice) as the lung emphysema model mimicking the chronic pulmonary inflammation in COPD. Acute inflammation was induced by intratracheal lipopolysaccharide administration, simulating COPD exacerbation. Mice were fed a diet containing 2% TJ-41 or a control diet. Taz CKO mice showed increased numbers of inflammatory cells in the bronchoalveolar lavage fluid compared to control mice. This effect was reduced by TJ-41 treatment. In the acute exacerbation model, TJ-41 mitigated the increased numbers of inflammatory cells in the bronchoalveolar lavage fluid and attenuated lung inflammation in histopathological studies. Additional in vitro experiments using the human macrophage cell line U-937 demonstrated that lipopolysaccharide-induced tumor necrosis factor-alpha expression was significantly downregulated by TJ-41. These results suggest that TJ-41 has anti-inflammatory effects in lung emphysema both in the chronic phase and during an acute exacerbation. In conclusion, our study sheds light on the anti-inflammatory effects of TJ-41 in lung emphysema. This establishes its potential as a new anti-inflammatory therapy and a preventive medicine for exacerbations during the long-time maintenance of COPD patients.</p>

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