“利咽”功效关联的金果榄质量标志物分析  

Quality Marker(Q-marker)of Tinosporae Radix Associated with Efficacy of"Relieving Sore Throat"

作　　者：卢丽洁 吴清华[1] 朱兴龙 黄旭龙 饶华楠 鲜彬 文飞燕 周涛 魏民 刘三波 裴瑾[1] LU Lijie;WU Qinghua;ZHU Xinglong;HUANG Xulong;RAO Huanan;XIAN Bin;WEN Feiyan;ZHOU Tao;WEI Min;LIU Sanbo;PEI Jin(School of Pharmacy,State Key Laboratory of Southwestern Chinese Medicine Resource,Chengdu University of Traditional Chinese Medicine(TCM),Chengdu 611137,China;China Resources Sanjiu Medical&Pharmaceutical Co.Ltd.,Shenzhen 518110,China;China Resources Sanjiu(Huangshi)Pharmaceutical Co.Ltd.,Huangshi435003,China)

机构地区：[1]成都中医药大学药学院,西南特色中药资源国家重点实验室,成都611137 [2]华润三九医药股份有限公司,广东深圳518110 [3]华润三九(黄石)药业有限公司,湖北黄石5435003

出　　处：《中国实验方剂学杂志》2023年第13期140-150,共11页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医药人函[2019]41号);四川省科技计划重点研发项目(2020YFN0152,2021YFYZ0012-5,2022YFS0582);四川省中医药发展服务中心-中医药产业发展重大项目(第九包)(510201202109711)。

摘　　要：目的基于超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q-TOF-MS)技术、多元统计分析和网络药理学技术研究金果榄的“利咽”质量标志物(Q-Marker)。方法首先采用UPLC-Q-TOF-MS技术辨识18批金果榄中的主要化学成分。在此基础上,一方面采用主成分分析和正交偏最小二乘法判别分析筛选出造成组间差异的主要标志性成分;另一方面利用网络药理学技术预测潜在“利咽”成分,并对多元统计分析和网络分析所得化合物交集与核心靶点进行分子对接,验证质量标志物准确性。结果UPLC-Q-TOF-MS共鉴定出金果榄中17个化合物,包括生物碱类、二萜内酯类、甾醇类等类型化合物。基于多元统计分析方法寻找到5个主要差异性成分,分别为非洲防己碱、药根碱、巴马汀、蝙蝠葛任碱和古伦宾。基于网络分析筛选出四氢巴马汀、巴马汀、蝙蝠葛任碱、去氧黄藤苦素、neoechinulin A、古伦宾共6个化合物为金果榄的潜在“利咽”成分;通过白细胞介素-6、表皮生长因子受体、前列腺素G/H合成酶2、基质金属蛋白酶-9和原癌基因酪氨酸蛋白激酶等关键靶点,以及乙型肝炎、甲型流感、人类嗜T细胞病毒感染、人巨细胞病毒感染和新型冠状病毒肺炎等通路发挥“利咽”功效。多元统计分析和网络分析共同预测所得金果榄中的潜在活性成分包括巴马汀、蝙蝠葛任碱和古伦宾,与6个核心靶点分子对接活性较好,可作为金果榄的“利咽”Q-Marker。结论该研究初步预测了金果榄的“利咽”质量标志物,有利于建立关联药效的金果榄质量标准,为完善该药材的质量评价体系提供参考。Objective To study the potential quality marker(Q-marker)of Tinosporae Radix associated with efficacy of"relieving sore throat"based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS),multivariate statistical analysis(MSA),and network pharmacology.Method UPLC-Q-TOF-MS was used to identify the main chemical components in 18 batches of Tinosporae Radix.On this basis,principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA)were employed to screen out the main marker components that caused differences between groups.Moreover,network pharmacology technology was applied to predict the potential"sore throat-relieving"components,and the molecular docking between the common components resulting from MSA and network pharmacology and the core targets was carried out to verify the marker components.Result A total of 17 compounds,including alkaloids,diterpenoid lactones,and sterols,were identified by UPLC-Q-TOF-MS.Five main differential components were found by MSA:Columbamine,jatrorrhizine,palmatine,menisperine,and columbin.Network pharmacology analysis yielded six compounds:tetrahydropalmatine,palmatine,menisperine,fibleucin,neoechinulin A,and columbin which were selected as potential"sore throat-relieving"components of Tinosporae Radix.They may relieve sore throat by acting on interleukin-6,epidermal growth factor receptor,prostaglandin G/H synthase 2,matrix metalloproteinase-9,proto-oncogene tyrosine-protein kinase Src and other targets,and regulating Hepatitis B,influenza A,human T-cell virus infection,human cytomegalovirus infection,coronavirus disease-2019,and other signaling pathways.The common active components in Tinosporae Radix resulting from MSA and network pharmacology analysis were palmatine,menisperine,and columbin,which had high binding affinity with six core targets and can be used as the Q-marker components of Tinosporae Radix in"relieving sore throat".Conclusion This study predicts the"sore throat-relieving"Q-mark

关 键 词：金果榄 利咽 超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q-TOF-MS) 多元统计分析 网络药理学 质量标志物 

分 类 号：R284.2[医药卫生—中药学] R285[医药卫生—中医学] R289R22R2-031R33