College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea.
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.
Phytomedicine. 2019 Jun;59:152777. doi: 10.1016/j.phymed.2018.11.037. Epub 2018 Dec 1.
Cigarette smoke (CS) is a major contributor to the high incidence of chronic obstructive pulmonary disease (COPD) featured as chronic inflammation and airway obstruction. Mahuang-Tang is a traditional polyherbal mixture composed of four different herbs. It is widely used in Asia as a remedy for allergic reaction and inflammation.
We investigated the effects of a modificated Mahuang-Tang water extract (MTWE) against airway inflammation caused by CS and lipopolysaccharide (LPS) in mice and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells.
CS exposed to animals for 1 h per day from day 1 to day 7 and treated with LPS intranasally on day 4. One hour before CS exposure, animals were received MTWE (50 or 100 mg/kg) by oral gavage. Inflammatory cell count and cytokines levels were measured in the bronchoalveolar lavage fluid. Expression levels of matrix metalloprotease-9 (MMP-9) and extracellular signal-regulated kinase (Erk) were analyzed by western blotting.
MTWE markedly decreased the neutrophil and other inflammatory cell counts in the bronchoalveolar lavage fluid and reduced proinflammatory mediators as evidenced by the decreases in inflammatory cell recruitment in lung tissue. Furthermore, MTWE meaningfully declined MMP-9 expression and reduced the Erk phosphorylation, caused by the CS and LPS exposure. In in vitro experiments, MTWE suppressed the elevated expression of proinflammatory cytokines induced by CSC treatment. MTWE reduced Erk phosphorylation and MMP-9 expression in CSC-stimulated H292 cells.
Overall, MTWE effectively inhibited the pulmonary inflammation and MMP-9 expression caused by the CS and LPS exposure, which was closely involved in suppression of Erk phosphorylation. These results suggest that MTWE possesses a potential for the treatment of COPD.
香烟烟雾(CS)是导致慢性阻塞性肺疾病(COPD)高发的主要因素,其特征为慢性炎症和气道阻塞。麻黄汤是一种由四种不同草药组成的传统复方草药。它在亚洲被广泛用作过敏反应和炎症的治疗方法。
我们研究了改良麻黄汤水提取物(MTWE)对 CS 和脂多糖(LPS)引起的小鼠气道炎症以及 CS 刺激的 NCI-H292 细胞的影响。
CS 暴露于动物中,每天 1 小时,从第 1 天到第 7 天,并在第 4 天通过鼻腔内给予 LPS。在 CS 暴露前 1 小时,动物通过口服灌胃给予 MTWE(50 或 100mg/kg)。通过支气管肺泡灌洗测量炎症细胞计数和细胞因子水平。通过 Western blot 分析基质金属蛋白酶-9(MMP-9)和细胞外信号调节激酶(Erk)的表达水平。
MTWE 显著降低了支气管肺泡灌洗液中的中性粒细胞和其他炎症细胞计数,并减少了炎症细胞在肺组织中的募集,从而降低了促炎介质的水平。此外,MTWE 显著降低了 CS 和 LPS 暴露引起的 MMP-9 表达,并减少了 Erk 磷酸化。在体外实验中,MTWE 抑制了 CS 处理引起的促炎细胞因子的升高表达。MTWE 降低了 CSC 刺激的 H292 细胞中 Erk 磷酸化和 MMP-9 表达。
总体而言,MTWE 有效抑制了 CS 和 LPS 暴露引起的肺部炎症和 MMP-9 表达,这与抑制 Erk 磷酸化密切相关。这些结果表明 MTWE 具有治疗 COPD 的潜力。