高效液相色谱法同时测定理中丸中7种成分含量及其治疗脾胃虚寒型胃病的作用靶点预测  

Simultaneous Determination of Seven Components in Lizhong Pills by HPLC and Prediction of Their Targets of Action in the Treatment of Gastric Diseases with Deficiency Cold in Spleen and Stomach

作　　者：王俏俏 黄娜娜 李俊 杨朝磊 王生凡 刘绍科 WANG Qiaoqiao;HUANG Nana;LI Jun;YANG Chaolei;WANG Shengfan;LIU Shaoke(School of Chinese Materia Medica,Yunnan University of Chinese Medicine,Kunming,Yunnan,China 650500;Yunnan Provincial Engineering Research Center for Ethnic Traditional Health Preservation Theories and Health Products,Kunming,Yunnan,China 650500;Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.,Nanjing,Jiangsu,China 210000;Expert Workstation of Kuang Haixue,Kunming,Yunnan,China 650500;Yongde County People′s Hospital,Lincang,Yunnan,China 677600)

机构地区：[1]云南中医药大学中药学院,云南昆明650500 [2]云南省民族特色养生理论与健康产品工程研究中心,云南昆明650500 [3]正大天晴药业集团股份有限公司,江苏南京210000 [4]云南省匡海学专家工作站,云南昆明650500 [5]云南省永德县人民医院,云南临沧677600

出　　处：《中国药业》2025年第7期29-35,共7页China Pharmaceuticals

基　　金：云南省院士专家工作站项目[202305AF150029]。

摘　　要：目的建立同时测定理中丸中7种活性成分含量的高效液相色谱(HPLC)法,并预测其治疗脾胃虚寒型胃病的作用靶点。方法色谱柱为Ultimate XB-C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.15%甲酸溶液(梯度洗脱),流速为0.8 m L/min,检测波长为260 nm,柱温为25℃,进样量为10μL。在Pharm Mapper数据库中检索各活性成分相关靶点,在Gene Cards数据库中筛选疾病靶点;通过Venny 2.1.0平台筛选活性成分与疾病的共有靶点,通过String数据库构建蛋白-蛋白互作(PPI)网络,通过Metascape数据库进行基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析,通过Cystoscape 3.8.2软件构建活性成分-共有靶点通路网络,并筛选核心靶点。结果5-羟甲基糠醛、色氨酸、党参苷Ⅰ、芹糖甘草苷、甘草苷、党参炔苷、甘草酸分别在各自质量浓度范围内与峰面积积分值线性关系良好(R2≥0.9992,n=6);精密度、稳定性、重复性试验的RSD均小于3.0%;平均加样回收率为97.48%~101.11%,RSD为2.01%~2.59%(n=9)。共获得疾病靶点3080个,活性成分-疾病共有靶点232个,核心靶点包括SRC、PI3K调节亚基1(PIK3R1)、生长因子受体结合蛋白2(GRB2)、Akt1、表皮生长因子受体(EGFR)、热休克蛋白90型αA1(HSP90AA1)、蛋白质络氨酸磷酸酶N11(PTPN11)、雌激素受体1(ESR1)、丝裂原活化蛋白激酶1(MAPK1)、丝裂原活化蛋白激酶8(MAPK8)。GO功能分析获得条目643条,包括生物学过程553条、分子功能48条、细胞组分(CC)42条。KEGG通路富集分析共得到145条信号通路,主要包括癌症中的蛋白聚糖、Ras、病灶黏附、磷脂酰肌醇-3-激酶/丝氨酸-苏氨酸蛋白激酶、内分泌抵抗等信号通路。结论所建立的方法操作简单、定量准确、重复性好,可用于同时测定理中丸中多种成分的含量。网络药理学预测了理中丸治疗脾胃虚寒型胃病的核心靶点及主要通路,为理中丸的质量控制及临床使�Objective To establish a high-performance liquid chromatography(HPLC)method for the simultaneously determination of of seven active components in Lizhong Pills,and to predict their targets of action in the treatment of gastric diseases with deficiency cold in spleen and stomach.Methods The chromatographic column was Ultimate XB-C18 column(250 mm×4.6 mm,5µm),the mobile phase was acetonitrile-0.15%formic acid solution(gradient elution),the flow rate was 0.8 mL/min,the detection wavelength was 260 nm,the column temperature was 25℃,and the injection volume was 10µL.The targets related to each active component in the PharmMapper database were searched,the disease targets in the GeneCards database were screened,the common targets among active components and diseases were screened by the Venny 2.1.0 platform,and the protein-protein interaction(PPI)network was constructed by the String database.The gene ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by the Metascape database.The active ingredient-common target pathway network was constructed and core targets were screened by the Cystscape 3.8.2 software.Results The 5-hydroxymethylfurfural,tryptophan,tangshenosideⅠ,liquiritin apioside,liquiritin,lobetyolin,and glycyrrhizic acid in Lizhong Pills showed good linear relationships with peak area integral values within their respective mass concentration ranges(R2≥0.9992,n=6).The RSDs of precision,stability,and repeatability tests were all lower than 3.0%.The average recoveries of the above seven components were in the range of 97.48%-101.71%,with RSDs of 2.01%-2.59%(n=9).A total of 3080 disease targets were obtained,including 232 active component-disease targets.The core targets included SRC,PIK3R1,GRB2,Akt1,EGFR,HSP90AA1,PTPN11,ESR1,MAPK1,and MAPK8.GO functional analysis obtained 643 items,including 553 biological processes(BP),48 molecular functions(MF),and 42 cellular components(CC).KEGG pathway enrichment analysis obtained 145 signaling

关 键 词：理中丸 活性成分 含量测定 脾胃虚寒型胃病 作用靶点 高效液相色谱法 网络药理学 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]