The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema
The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema
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DOI：
10.1248/bpb.b20-00556
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发表时间：
2021-01-01
影响因子：
2
通讯作者：
Jo, Taisuke
中科院分区：
文献类型：
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作者：
Isago, Hideaki;Mitani, Akihisa;Jo, Taisuke
慢性阻塞性肺疾病是一种全身性炎症性疾病。它通常会导致体重减轻，这被认为是一个糟糕的预后因素。据报道，一种日本草药Kampo药物Hochuekkito(TJ-41)可以预防COPD患者的全身炎症和体重减轻，但其潜在的生物学机制仍不清楚。在本研究中，我们利用肺气肿的小鼠模型研究了TJ-41在体内的作用。我们使用肺上皮细胞特异性Taz条件性基因敲除小鼠(Taz CKO小鼠)作为模拟COPD慢性肺部炎症的肺气肿模型。通过气管内注射脂多糖诱导急性炎症反应，模拟COPD加重。小鼠饲喂含2%TJ-41的饲料或对照饲料。与对照组相比，TAZ CKO小鼠的支气管肺泡灌洗液中的炎性细胞数量增加。这种作用被TJ-41处理后减弱。在急性加重模型中，TJ-41减轻了支气管肺泡灌洗液中炎性细胞数量的增加，并减轻了组织病理学研究中的肺部炎症。此外，使用人巨噬细胞系U-937进行的体外实验表明，TJ-41显著下调了内毒素诱导的肿瘤坏死因子-α的表达。提示TJ-41对肺气肿慢性期和急性加重期均有抗炎作用。综上所述，我们的研究为TJ-41在肺气肿中的抗炎作用提供了线索。这确立了它作为一种新的抗炎疗法和预防COPD患者长期维持期间病情恶化的药物的潜力。
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.