Screening hepatoprotective effective components of Lonicerae japonica Flos based on the spectrum-effect relationship and its mechanism exploring

Lonicerae japonicae Flos(LF)is a kind of healthcare food with hepatoprotective function.This study was designed to explore the spectrum-effect relationships between UPLC fingerprints and the hepatoprotective effects of LF.Fingerprints of ten batches of LF were established by UPLC-PDA.The inhibitory levels of AST and ALT were used as pharmacological indexes,and secoxyloganin,isochlorogenic acid A and isochlorogenic acid C were screened as hepatoprotective active compounds by grey relational analysis(GRA)and partial least squares regression analysis(PLSR).Caspase-3 was obtained by network pharmacology as a key target of hepatoprotective active compounds.Molecular docking is used to explore the interaction between small molecules and proteins.This work provided a general model of the combination of UPLC-PDA and hepatoprotective effect to study the spectrum-effect relationship of LF,which can be used to considerable methods and insight for the fundamental research of the material basis of similar healthcare food.

基于谱效整合分子对接技术研究瓜蒌子及其壳、仁抗凝血的物质基础及作用机制

基于谱效整合分子对接技术研究瓜蒌子及其壳、仁抗凝血的物质基础及机制。建立瓜蒌子及其壳、仁的HPLC指纹图谱,测定瓜蒌子及其壳、仁2个剂量组(5、30 g·kg;)抗小鼠凝血生化指标凝血酶原时间(prothrombin time,PT)及活化部分凝血活酶时间(activated partial thromboplastin time,APTT),以Matlab语言采用邓氏关联度计算法分析瓜蒌子及其壳、仁抗凝血的谱效关系和物质基础,获得共有药效成分群。利用TCMSP、SwissTargetPrediction、GenCLiP3、GeneCards、DAVID等数据库,获取共有药效成分群与疾病“coagulation”的共有靶点蛋白,进行信号通路及生物学功能注释分析并利用SYBYL-X 2.1.1软件对共有药效成分群抗凝血的主要分子机制加以验证。瓜蒌子及其壳、仁的谱-效关联度与给药剂量呈正相关,各成分抗凝血作用的贡献程度并不一致即发挥抗凝血作用的物质基础不同,但存在共有药效成分群即共同物质基础,如腺嘌呤(3号峰)、尿嘧啶(4号峰)、次黄嘌呤(6号峰)、黄嘌呤(9号峰)、腺苷(11号峰)(简称腺嘌呤等)。网络药理学研究表明,腺嘌呤等可作用于NOS3、KDR、PTGS2等多个靶点蛋白通过VEGF signaling pathway等多条通路发挥抗凝血作用,涉及proteolysis等生物功能及cytosol等细胞组成和分子功能。分子对接结果表明,腺嘌呤等与NOS3(PDB ID:1D0C)、KDR(PDB ID:5AMN)、PTGS2(PDB ID:4COX)的结合自由能均≤-5 kJ·mol^(-1),分子对接构象稳定。谱效整合分子对接技术可用于中药复杂化学信息和生物学信息的优化、虚拟筛选与验证。瓜蒌子及其壳、仁有抗凝血作用的共同物质基础且可通过多靶点、多通路发挥抗凝血作用。