吸烟和大气污染导致我国慢性阻塞性肺疾病(COPD)高发。“清痰瘀”与“抑制氧化应激和炎症反应”分别为中西医治疗COPD主要原则。锦灯笼清肺治咳、利咽化痰，治疗气道炎症疗效确凿。申请人前期研究发现，锦灯笼双重抑制氧化应激和炎症反应的作用显著，与中西医治疗COPD的原则相符，有成为干预COPD新药的潜力；其活性成分复杂、结构多样、种类繁多，除黄酮外，其他双重抑制氧化应激和炎症反应的活性成分尚未明确。本申请项目拟：（1）开展锦灯笼双重抑制氧化应激和炎症反应的活性成分追踪分离与构效关系分析；（2）针对氧化应激和炎症反应关键调控通路，揭示至少三种不同结构类型强活性成分的作用机制和多靶点协同作用；（3）在细胞和动物水平，开展活性成分干预COPD的有效性研究。研究结果将揭示锦灯笼药效物质基础，完善其中药理论和传统应用的生物学依据，为研发新型抗COPD药物奠定基础，对抗COPD中药的基础研究具有重要意义。

Smoking and air pollution give rise to a high incidence of chronic obstructive pulmonary disease (COPD) in China. ‘Sweeping stagnate and sputum’ and ‘inhibitions of oxidative stress and inflammation’ are the therapeutic strategies for traditional Chinese medicines and western medicines, respectively. Calyx seu Fructus Physalis is a traditional Chinese medicine with the function of ‘sweeping stagnate and sputum’, and demonstrates a satisfying therapeutic effect on airway inflammation. Previous study indicated that Calyx seu Fructus Physalis possessed potent inhibitory effects against oxidative stress and inflammation, is consistent with therapeutic strategies of traditional Chinese medicines and modern medicines, and has a potential as new COPD therapeutic agent. It contained diverse bioactive substances. The mechanism on inhibition of oxidative stress and inflammation of these ingredients, with exception of flavonoids, are still unknown. Based on these findings, the work will be carried out as follows. (i) Bio-guided isolation and structure elucidation of ingredients with inhibitory effects against oxidative stress and inflammation, and illustrating the relationship between these two bioactivities and chemical ingredients. (ii) Based on the key oxidative stress- and inflammation- regulating signaling pathways, illustrating the molecular mechanism of diverse bioactive substances, and discussing the synergic mechanism of different structural skeleton. (iii) Evaluating the therapeutic effect of bioactive substances against COPD using cell and animal models, and discussing its druggability. The results of our research will illustrate its bioactive substances of Calyx seu Fructus Physalis, give the biological evidences for its traditional uses, provide a research basis for research and development of new COPD drugs, and have significance for the strategy of finding COPD therapeutic agents from traditional Chinese medicines.