基于代谢组学的桔梗总皂苷镇咳祛痰作用机制研究  

The antitussive and expectorant mechanism of Platycodon total saponins based on metabonomics

作　　者：王新红 张迟 周丽 曾金祥 任玲玲 毛竹 袁恩 周立分 WANG Xin-hong;ZHANG Chi;ZHOU Li;ZENG Jin-xiang;REN Ling-ling;MAO Zhu;YUAN En;ZHOU Li-fen(Research Center of Traditional Chinese Medicine Resources and Ethnic Minority Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Large Precision Instrument Sharing Service Center,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学中药资源与民族药研究中心,江西南昌330004 [2]江西中医药大学大型精密仪器共享服务中心,江西南昌330004

出　　处：《药学学报》2022年第3期757-765,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金(81860685,82160736);江西中医药大学中药双一流学科建设项目(JXSYLXK-ZHYAO033)。

摘　　要：利用UHPLC-Q-TOF/MS代谢组学技术,分析桔梗总皂苷对浓氨水引咳模型以及酚红排泄模型小鼠血清内源性代谢物代谢紊乱的调控作用,明确桔梗总皂苷发挥镇咳与祛痰作用的代谢调控途径。经江西中医药大学实验动物伦理委员会审议同意并批准后(批准号:JZLLSC-20190235),将小鼠随机分成正常组、模型组、阳性药组和桔梗总皂苷给药组,通过浓氨水引咳实验和酚红排泄实验来评价桔梗总皂苷的镇咳与祛痰药效。采用UHPLC-Q-TOF/MS对浓氨水引咳模型以及酚红排泄模型小鼠血清代谢物进行鉴定,并采用主成分分析、正交偏最小二乘判别分析进行多元分析,通过变量投影重要性值和t检验结果来筛选差异代谢物,利用Metaboanalyst平台分析差异代谢物的代谢通路。结果显示桔梗总皂苷能显著延长浓氨水引咳模型中小鼠的咳嗽潜伏期和咳嗽次数,能显著增加酚红排泄模型中小鼠的酚红排泄量。通过UHPLC-Q-TOF/MS共鉴定出19种与咳嗽相关的差异代谢物,桔梗总皂苷能显著回调其中的16种;鉴定出17种与排痰相关的差异代谢物,桔梗总皂苷能回调其中的17种。代谢通路分析显示亚油酸代谢、花生四烯酸代谢和甘油磷脂代谢为其改善浓氨水引咳模型小鼠血清代谢紊乱的主要途径;亚油酸代谢,苯丙氨酸、酪氨酸和色氨酸的生物合成,花生四烯酸代谢,苯丙氨酸代谢和α-亚麻酸代谢为其改善酚红排泄模型小鼠血清代谢紊乱的主要途径。本研究综合多种技术首次阐明桔梗总皂苷发挥镇咳与祛痰作用的代谢调控途径。UHPLC-Q-TOF/MS metabonomics technology was used to clarify the metabolic regulation pathways by which Platycodon total saponins(PTS) exert antitussive and expectorant effects in a mouse cough model, in which coughing is induced by concentrated ammonia, and in a phenol red excretion model. After approval by the Experimental Animal Ethics Committee of Jiangxi University of Chinese Medicine(Approval No.JZLLSC-20190235), the mice were randomly divided into a normal group, a model group, a positive drug group and a PTS group. Endogenous metabolites in mouse serum were identified by UHPLC-Q-TOF/MS. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used for multivariate analysis. Metabolic pathways were analyzed by the Metaboanalyst platform. The results show that PTS can significantly prolong the cough latent period and cough frequency of mice, and significantly increase phenol red excretion. UHPLC-Q-TOF/MS identified 19 metabolites related to cough, and PTS significantly decreased 16 of them;17 metabolites related to expectoration were identified, and PTS decreased the levels of all.Metabolic pathway analysis showed that linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism were the main pathways involved in serum metabolite changes in this mouse cough model. Linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism and α-linolenic acid metabolism were the main pathways involved in serum metabolite changes in the phenol red excretion model. This study is the first to elucidate the regulation of antitussive and expectorant metabolic pathways and the effect of PTS on these pathways.

关 键 词：桔梗总皂苷 镇咳 代谢组学 作用机制 

分 类 号：R917[医药卫生—药物分析学]