目的 在化学成分指引下对川贝母Fritillaria cirrhosa茎叶的药效作用进行研究，为川贝母茎叶的综合开发利用提供依据。方法 采用超高效液相色谱-串联质谱（UPLC-MS/MS）方法检测川贝母茎叶及鳞茎中的化学成分，比较两者的相似性，推测川贝母茎叶的功效。选择两者有代表性的30个共有化学成分，采用网络药理学方法研究川贝母茎叶对肺炎、支气管炎、支气管哮喘的作用靶点及其机制，并通过动物实验对其进行药效验证。结果 检测得到川贝母茎叶与鳞茎共有成分759个，筛选前30种主要化学成分，搜索得到药物潜在靶点共1816个；检索得到支气管哮喘靶点2358个、肺炎靶点5014个、支气管炎靶点1964个；川贝茎叶对肺炎、支气管炎、支气管哮喘的共同靶点有333个，基因本体（gene ontology，GO）功能富集分析得到GO条目762个（P<0.05），其中生物过程条目617个、细胞组成条目50个、分子功能条目95个，分别占81%、7%、12%；涉及的京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）信号通路主要有代谢通路和癌症通路等。氨水引咳实验及化痰实验结果显示，茎叶水提组与可待因组和急支糖浆组比较，咳嗽次数无显著差异，均能显著增加小鼠酚红排泌量。结论 川贝母茎叶与鳞茎化学成分基本相同，可能与鳞茎具有相似的功效，川贝茎叶中的异鼠李素-7-O-葡糖苷（isorhamnetin-7-O-glucoside）、精胺（spermine）、N-乙酰基-L-色氨酸（N-acetyl-L-tryptophan）、γ-亚麻酸（γ-linolenic acid）等成分可能通过CCND1、EP300、CDK2、INS、EGF、CDC42、DNMT1、PARP1等靶点，调节代谢通路和癌症通路等信号通路，发挥其止咳化痰作用，可为川贝母茎叶的进一步开发利用提供依据。

Objective Under the exploration of the chemical composition, the pharmacodynamic reaction of the stems and leaves of Chuanbeimu (Fritillaria cirrhosa) was studied, which provides a basis for the comprehensive development and utilization of the stems and leaves of F. cirrhosa. Methods The UPLC-MS/MS method was used to detect the chemical components of the stems, leaves and bulbs of F. cirrhosa, then the similarity of the chemical components was compared and its efficacy was speculated. Under the basis of the 30 representative common chemical components of the stems, leaves and bulbs of F. cirrhosa and the guidance of network pharmacology, the targets and mechanisms of the stems and leaves of F. cirrhosa against pneumonia, bronchitis, and bronchial asthma were studied, and its efficacy was verified by animal experiments. Results A total of 759 constituents in stems, leaves and bulbs of F. cirrhosa were identified by UPLC-MS/MS method, and a total of 1816 potential drug targets were obtained by screening the top 30 main chemical components; The number of targets for bronchial asthma was 2358, the number of targets for pneumonia was 5014, and the number of targets for bronchitis was 1964; The stems and leaves of F. cirrhosa had 333 common targets for pneumonia, bronchitis and bronchial asthma. GO functional enrichment analysis obtained 762 GO entries (P < 0.05), which included 617 biological process (BP) entries, 50 cell composition (CC) entries and 95 molecular function (MF) entries, accounting for 81%, 7% and 12% respectively; KEGG signaling pathways involved mainly included metabolic pathways and pathways in cancer, etc. The results of the ammonia water cough and the phlegm-resolving experiment showed that there was no significant difference in the number of coughs between the stem and leaf water extraction group and the codeine group and the emergency syrup group, and both of them significantly increased the mice phenol red excretion. Conclusion The stems and leaves of F. cirrhosa have basically the same chemical composition as the bulbs, and may have similar effects with the bulbs. The isorhamnetin-7-O-glucoside, spermine, N-acetyl-L-tryptophan, γ-linolenic acid and other ingredients may regulate metabolic pathways and pathways in cancer and other signaling pathways through CCND1, EP300, CDK2, INS, EGF, CDC42, DNMT1, PARP1 and other targets, exerting their cough-reducing and phlegm-reducing effects, which can provide the references for the further development and utilization of the stems and leaves of F. cirrhosa.

R285;R284.1

“十三五”国家重点研发计划项目（2017YFC1701900）；四川省科技成果转移转化示范项目2020ZHCG0073）；四川省科学技术厅2020年省级科技计划项目（20YYJC1839）；2020广西壮瑶药重点实验室开放课题（GXZYKF2020-04）