Lu Qinfeng, Chen Zhu, Mu Bai-Xiang, Wang Bo-Han, Feng Fanchao, Zhao Jun, He Hailang, Wei Yu
Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China.
Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China.
J Ethnopharmacol. 2025 Sep 25;353(Pt A):120363. doi: 10.1016/j.jep.2025.120363. Epub 2025 Aug 5.
COPD, marked by coughing, sputum production, and wheezing, is categorized as "Lung Distension" in Traditional Chinese Medicine (TCM). The combined use of Suzi Jiangqi Decoction and Sanzi Yangqin Decoction, known as Jia Wei Su Zi Jiang Qi Formula (JWSZJQF), is a common treatment for Lung Distension with phlegm accumulation in the lungs. It is particularly effective for symptoms like excessive phlegm and chest tightness. However, the specific active components of JWSZJQF and their molecular mechanisms in addressing mucus hypersecretion in COPD remain unclear, requiring further investigation and validation.
This study aims to identify the potential targets and signaling pathways of JWSZJQF in treating COPD-associated mucus hypersecretion using UHPLC-Q-Orbitrap MS/MS, network pharmacology, and in vitro experimental verification.
All plant names were verified through WorldFloraOnline (www.worldFloraonline.org) and MPNs (http://mpns.kew.org). First, the effective components of JWSZJQF were identified and analyzed using UHPLC-Q-Orbitrap MS/MS, supplemented by data from TCMSP. Network pharmacology analysis was used to determine the potential targets and pathways of JWSZJQF in COPD treatment. A mucus hypersecretion cell model was created using IL-17 cytokine, and the effectiveness of JWSZJQF in reducing mucus hypersecretion was assessed through immunofluorescence assay, Western blotting, and quantitative real-time polymerase chain reaction (qPCR). Lastly, a prospective study was conducted to collect data from 30 inpatients with AECOPD between September 2023 and July 2024. Serum samples before and after treatment were analyzed to validate the findings.
A total of 864 active components were identified, with 79 potential COPD therapeutic targets confirmed based on the top 30 active components, including TNF, IL-6, and AKT1. The involved KEGG pathways included the IL-17 and NF-κB signaling pathways. In vitro experiments showed that JWSZJQF inhibited mucin (MUC5AC) secretion at both mRNA and protein levels. Additionally, JWSZJQF modulated i-κBα and p65 expression in the NF-κB pathway. Compared to the control group, patients treated with JWSZJQF exhibited lower levels of IL-17 and MUC5AC in their serum.
This study preliminarily explored the mechanisms of JWSZJQF in treating COPD-associated mucus hypersecretion through UHPLC-Q-Orbitrap MS/MS, network pharmacology, in vitro experiments, and clinical observation. The main active components and potential targets were identified, laying a scientific foundation for further research.
慢性阻塞性肺疾病（COPD）以咳嗽、咳痰和喘息为特征，在传统中医（TCM）中被归类为“肺胀”。苏子降气汤和三子养亲汤合方，即加味苏子降气方（JWSZJQF），是治疗肺胀伴痰浊内阻的常用方剂。它对痰量过多和胸闷等症状特别有效。然而，JWSZJQF的具体活性成分及其在解决COPD黏液高分泌中的分子机制仍不清楚，需要进一步研究和验证。
本研究旨在通过超高效液相色谱-四极杆-轨道阱串联质谱（UHPLC-Q-Orbitrap MS/MS）、网络药理学和体外实验验证，确定JWSZJQF治疗COPD相关黏液高分泌的潜在靶点和信号通路。
所有植物名称均通过世界植物在线（www.worldFloraonline.org）和植物名称索引（http://mpns.kew.org）进行核实。首先，使用UHPLC-Q-Orbitrap MS/MS对JWSZJQF的有效成分进行鉴定和分析，并辅以中药系统药理学数据库与分析平台（TCMSP）的数据。采用网络药理学分析确定JWSZJQF在COPD治疗中的潜在靶点和途径。使用白细胞介素-17（IL-17）细胞因子建立黏液高分泌细胞模型，并通过免疫荧光测定、蛋白质印迹和定量实时聚合酶链反应（qPCR）评估JWSZJQF在减少黏液高分泌方面的有效性。最后，进行一项前瞻性研究，收集2023年9月至2024年7月期间30例慢性阻塞性肺疾病急性加重期（AECOPD）住院患者的数据。对治疗前后的血清样本进行分析以验证研究结果。
共鉴定出864种活性成分，基于前30种活性成分确认了79个潜在的COPD治疗靶点，包括肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）和蛋白激酶B1（AKT1）。涉及的京都基因与基因组百科全书（KEGG）通路包括IL-17和核因子κB（NF-κB）信号通路。体外实验表明，JWSZJQF在mRNA和蛋白质水平上均抑制黏蛋白（MUC5AC）的分泌。此外，JWSZJQF调节NF-κB通路中抑制蛋白κBα（I-κBα）和核转录因子p65的表达。与对照组相比，接受JWSZJQF治疗的患者血清中IL-17和MUC5AC水平较低。
本研究通过UHPLC-Q-Orbitrap MS/MS、网络药理学、体外实验和临床观察，初步探讨了JWSZJQF治疗COPD相关黏液高分泌的机制。确定了主要活性成分和潜在靶点，为进一步研究奠定了科学基础。
