慢阻肺是致死率最高的呼吸系统慢病，同时其药物研发的严重滞后，已成为人类健康的“沉默杀手”。中药莪术临床上具有确切的抗慢阻肺疗效，但主要以总提物入药，其药效物质成分与作用机制尚不明确，如何运用现代药理学技术阐明其药效物质基础及作用靶点-通路是本领域研究难题。本项目拟以莪术抗慢阻肺的中医药理论为指导，结合慢阻肺的现代病理调控机制，采用靶点-通路无偏袒的无标记细胞整合药理学技术构建慢阻肺最相关的肾上腺素能β2和毒蕈碱型胆碱能M3靶点-通路评价体系，同时借助自主研发的特色高效色谱分离纯化技术，高效追踪制备活性组分及成分；开展莪术抗慢阻肺的活性物质基础及其在β2和M3受体及下游通路的整合调控机制研究，总结不同活性成分的量效规律，建立成分-靶点-通路网络关系，最终揭示莪术抗慢阻肺的药效物质基础与靶点-通路整合作用机制，同时也为阐明中药临床疗效的科学内涵以及抗慢阻肺药物的研发提供理论依据和研究基础。

Chronic obstructive pulmonary disease (COPD) causes the highest fatality rate among chronic respiratory diseases, which has become a silent killer due to lack of anti-COPD drugs. Traditional Chinese medicine (TCM) Curcuma Kwangsiensis (C. Kwangsiensis) shows proved clinical efficacy in treating COPD when used in the form of total extract, which however leaves information unclear, such as effective components and mechanisms of the efficacy. It is a great challenge to elucidate the active components and target-pathway mechanisms by modern pharmacological techniques. To confront this challenge, based on TCM theory of C. Kwangsiensis treating COPD and modern pathological regulation mechanisms of COPD, this project will apply an unbiased cellular label-free integrative pharmacology (CLIP) technique to develop target-pathway systems composed by adrenergic β2 and muscarinic cholinergic M3 receptors. We will assay C. Kwangsiensis fractions on these two targets that are mostly related to COPD, and then use self-researched high-performance chromatographic separation and purification techniques to tract and prepare active components. Analyzing their integrative regulatory mechanisms on β2 and M3 target-pathway systems, we will summarize a concentration-activity relationship, and therefore establish a network of active components, targets and pathways. This project will clarify effective components and integrative mechanisms of C. Kwangsiensis treating COPD, providing theoretical foundation and research basis in revealing scientific significance of clinical efficacy and development of anti-COPD drugs.