A chinese herbal formula ameliorates COPD by inhibiting the inflammatory response via downregulation of p65, JNK, and p38
A chinese herbal formula ameliorates COPD by inhibiting the inflammatory response via downregulation of p65, JNK, and p38
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一种中药配方通过下调p65、JNK和p38抑制炎症反应来改善COPD
DOI：
10.1016/j.phymed.2021.153475
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发表时间：
2021-02-02
期刊：
影响因子：
7.9
通讯作者：
Liu, Xuefang
中科院分区：
文献类型：
--
作者：
Li, Jiansheng;Xie, Yang;Liu, Xuefang
背景资料：补肺益肾方是治疗慢性阻塞性肺疾病（COPD）的有效中药，目的：评价补肺益肾方的临床疗效，并探讨其作用机制。对照组66例采用西医常规治疗。通过对一项四中心、开放标签、随机对照的中医综合干预试验的数据进行亚组分析，评价了补阳还五汤的疗效。用补阳还五汤的关键活性分子（KAM）治疗COPD大鼠模型8周。结果：补阳还五汤治疗组COPD急性加重频率（p < 0.001）、持续时间（p = 0.028）、呼吸困难评分（p = 0.007）、6 min步行距离（p = 0.048）均明显降低。1秒用力肺活量（FVC）、1秒用力呼气量（FEV 1）和FEV 1占预计值的百分比（FEV1%）无差异。补肾益肺方能改善COPD大鼠的肺功能，包括潮气量、每分钟通气量、最大呼气流量、FVC、FEV0.1、FEV0.3及病理改变。KAM-BYF治疗显著降低血清和支气管肺泡灌洗液中白细胞介素6（IL 6）、肿瘤坏死因子α（TNF-α）、基质金属蛋白酶9（MMP 9）和MMP 12的水平。在气道上皮细胞中，KAM-BYF降低了TNF-α诱导的IL 8和IL 6的水平。最后，我们发现，KAM-BYF在COPD大鼠和BEAS-2Bs中的抗炎作用是通过抑制核因子-κ B（NF-κ B B）p65、c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶信号传导介导的。
Background: Bufei Yishen formula (BYF), a traditional Chinese medicine (TCM), is an effective therapeutic strategy for patients with chronic obstructive pulmonary disease (COPD).Purpose: To evaluate the efficacy of BYF and investigate its therapeutic mechanisms.Methods: A total of 134 patients completed the study: 68 patients treated by BYF combined with conventional Western medicine in the trial group; and 66 patients treated using conventional Western medicine in the control group. The efficacy of BYF was evaluated by a subgroup analysis of data obtained from a four-center, open-label, randomized controlled trial of comprehensive TCM interventions. A rat model of COPD was treated with the key active molecules (KAM) of BYF for 8 weeks. An in vitro model of COPD was also treated with KAM.Results: Patients treated with BYF had reduced frequency of acute exacerbation of COPD (p < 0.001) and duration (p = 0.028), dyspnea scale (p = 0.007), 6-min walking distance (p = 0.048). There were no differences observed in forced vital capacity in one second (FVC), forced expiratory volume in one second (FEV1), and FEV1 percentage of the predicted value (FEV1%). The five KAM of BYF (KAM-BYF) improved lung function, including tidal volume, minute ventilation, peak expiratory flow, FVC, FEV0.1, and FEV0.3, and pathological changes in COPD rats. Treatment with KAM-BYF markedly decreased the levels of interleukin 6 (IL6), tumor necrosis factora (TNF-alpha), matrix metalloproteinase 9 (MMP9), and MMP12 in serum and bronchial alveolar lavage fluid. In airway epithelial cells, KAM-BYF decreased the levels of TNF-alpha-induced IL8 and IL6. Finally, we discovered that the anti-inflammatory effects of KAM-BYF in COPD rats and BEAS-2Bs were mediated through inhibition of nuclear factor-kappaB (NF-kappa B) p65, c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase signaling.Conclusions: BYF exerts beneficial effects in patients with COPD via inhibition of inflammation.