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麻杏甘石汤对中性粒细胞性肺部炎症的治疗作用与抑制NF-κB和激活Nrf2有关。

Therapeutic effect of Mahaenggamseok-tang on neutrophilic lung inflammation is associated with NF-κB suppression and Nrf2 activation.

作者信息

Kim Kyun Ha, Lee Ji Yeon, Kwun Min Jung, Choi Jun-Young, Han Chang Woo, Ha Ki-Tae, Jeong Seung-Il, Jeong Han-Sol, Joo Myungsoo

机构信息

School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.

Department of Internal Medicine, Korean Medicine Hospital, Pusan National University, Yangsan 50612, Republic of Korea.

出版信息

J Ethnopharmacol. 2016 Nov 4;192:486-495. doi: 10.1016/j.jep.2016.09.040. Epub 2016 Sep 20.

DOI:10.1016/j.jep.2016.09.040
PMID:27660010
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Mahaenggamseok-tang (MHGST), an herbal formula in traditional Asian medicine, has been used to treat patients with various pulmonary diseases including common cold and influenza. However, the potential therapeutic effect of MHGST on acute lung injury (ALI), a leading cause of death worldwide, and the anti-inflammatory mechanisms of MHGST remained less understood.

MATERIALS AND METHODS

The methanol extract of MHGST was prepared and fingerprinted by HPLC. For the induction of ALI, C57BL/6 mice (n=5/group) received a single intraperitoneal (i.p.) injection of LPS. Referring to the dose for patients, two different amounts of MHGST were delivered in an aerosol to mouse lungs via trachea 2h after the i.p. LPS administration. Lung histology, bronchoalveolar lavage fluid, myeloperoxidase (MPO) activity, and the expression of inflammatory and Nrf2-dependent genes were analyzed to determine the effect of MHGST on lung inflammation. For mechanistic studies, western blotting and semi-quantitative RT-PCR were conducted using RAW 264.7 cells.

RESULTS

When administered 2h after the onset of ALI, MHGST relieved lung pathology characteristic to ALI, with decreases of neutrophil infiltration and MPO activity. While suppressing the expression of inflammatory genes, MHGST increased the expression of Nrf2-dependent genes in ALI mouse lungs. Concordantly, MHGST activated Nrf2 activity while suppressing NF-κB in RAW 264.7 cells.

CONCLUSION

MHGST suppressed neutrophilic lung inflammation, a hallmark of ALI, which was associated with the activation of anti-inflammatory Nrf2 and the suppression of pro-inflammatory NF-κB. Our results suggest that MHGST has a therapeutic potential against ALI.

摘要

民族药理学相关性

麻杏甘石汤(MHGST)是一种传统亚洲医学中的草药配方,已被用于治疗包括普通感冒和流感在内的各种肺部疾病患者。然而,MHGST对急性肺损伤(ALI)(全球主要死因之一)的潜在治疗作用以及MHGST的抗炎机制仍鲜为人知。

材料与方法

制备了MHGST的甲醇提取物并用高效液相色谱法进行指纹图谱分析。为诱导ALI,C57BL/6小鼠(每组n = 5)接受单次腹腔注射脂多糖(LPS)。参照患者剂量,在腹腔注射LPS后2小时,通过气管将两种不同剂量的MHGST以气雾剂形式输送至小鼠肺部。分析肺组织学、支气管肺泡灌洗液、髓过氧化物酶(MPO)活性以及炎症和Nrf2依赖性基因的表达,以确定MHGST对肺部炎症的影响。对于机制研究,使用RAW 264.7细胞进行蛋白质印迹和半定量逆转录 - 聚合酶链反应。

结果

在ALI发作后2小时给药时,MHGST减轻了ALI特有的肺部病理变化,中性粒细胞浸润和MPO活性降低。在抑制炎症基因表达的同时,MHGST增加了ALI小鼠肺中Nrf2依赖性基因的表达。同样,MHGST在RAW 264.7细胞中激活Nrf2活性,同时抑制NF - κB。

结论

MHGST抑制了ALI的标志性嗜中性肺部炎症,这与抗炎性Nrf2的激活和促炎性NF - κB的抑制有关。我们的结果表明,MHGST对ALI具有治疗潜力。

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