Zhang Fangbo, Guo Feifei, Liu Yang, Zhang Yi, Li Defeng, Yang Hongjun
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2022 Jun 8;13:903593. doi: 10.3389/fphar.2022.903593. eCollection 2022.
Chronic obstructive pulmonary disease (COPD) is the most common respiratory disease with high morbidity and mortality. Shema oral liquid (Shema) is a traditional Chinese medicine (TCM) approved for the treatment of respiratory diseases. Clinical applications have shown that Shema has antitussive, expectorant, and anti-asthmatic effects, but its definite efficacy to COPD is still unclear. This study aimed to explore the therapeutic capacity and potential mechanism of Shema in treatment of COPD. Network pharmacology was used to investigated the possible pharmacological mechanism of Shema against COPD. A rat model of lipopolysaccharide (LPS)-induced COPD was established to determine pulmonary ventilatory function, serum inflammatory cytokines, and pulmonary pathological change. Subsequently, tandem mass tag (TMT)-based quantitative proteomics was used to further reveal the therapeutic targets related with Shema against COPD. Western blot was finally performed to validate the expression of targeted proteins screened by proteomics research. Network pharmacology analysis indicated that Shema against COPD mainly inhibited the inflammation and affected the immune system. The animal experiment demonstrated that Shema treatment protected the lung tissue from LPS induced injury, inhibited the levels of serum inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, and improved the respiratory ventilatory function by upregulating forced expiratory volume in 0.1 s (FEV0.1), FEV0.3, forced vital capacity (FVC), and the ratios of FEV0.1 (0.3)/FVC. Proteomic analysis and western blot both proved that Shema inhibited the expression of DNA methyltransferase 1 (DNMT1) in the lung tissue. The therapeutic mechanism of Shema in treatment of COPD may involve inhibiting inflammatory response, improving pulmonary ventilatory function, and alleviating LPS-induced lung injury through regulating the expression of DNMT1. This study also shed light on the development of therapeutic strategies in treating COPD by intervening DNMT-related pathways.
慢性阻塞性肺疾病（COPD）是最常见的呼吸系统疾病，发病率和死亡率都很高。蛇麻草口服液（蛇麻草）是一种被批准用于治疗呼吸系统疾病的传统中药。临床应用表明，蛇麻草具有镇咳、祛痰和平喘作用，但其对COPD的确切疗效仍不明确。本研究旨在探讨蛇麻草治疗COPD的治疗能力和潜在机制。采用网络药理学研究蛇麻草抗COPD的可能药理机制。建立脂多糖（LPS）诱导的COPD大鼠模型，以测定肺通气功能、血清炎症细胞因子和肺病理变化。随后，基于串联质谱标签（TMT）的定量蛋白质组学被用于进一步揭示蛇麻草抗COPD的治疗靶点。最后进行蛋白质免疫印迹法验证蛋白质组学研究筛选出的靶向蛋白的表达。网络药理学分析表明，蛇麻草抗COPD主要通过抑制炎症反应和影响免疫系统发挥作用。动物实验表明，蛇麻草治疗可保护肺组织免受LPS诱导的损伤，抑制血清炎症细胞因子如白细胞介素（IL）-1β、IL-6、IL-8和肿瘤坏死因子（TNF）-α的水平，并通过上调0.1秒用力呼气量（FEV0.1）、FEV0.3、用力肺活量（FVC）以及FEV0.1（0.3）/FVC比值来改善呼吸通气功能。蛋白质组学分析和蛋白质免疫印迹法均证明蛇麻草可抑制肺组织中DNA甲基转移酶1（DNMT1）的表达。蛇麻草治疗COPD的机制可能包括抑制炎症反应通过调节DNMT1的表达，改善肺通气功能，减轻LPS诱导的肺损伤。本研究还为通过干预与DNMT相关的途径来制定COPD治疗策略提供了思路。
