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藤黄健骨胶囊质控成分定量分析方法建立及潜在作用机制预测
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          周 霖    1, 2* ,王肖辉 ,孙 志 ,薛连平 ,金建文 ,武 婧 ,李晓静 ,郑天元 ,张晓坚 (1.郑州大学第一附属医
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          院药学部,郑州 450052;2.中南大学资源加工与生物工程学院,长沙 410000;3.郑州大学第一附属医院超声
          科,郑州 450052;4.陕西丽彩药业有限公司,陕西 咸阳 712000)
          中图分类号  R917;R965      文献标志码  A      文章编号  1001-0408(2022)22-2743-05
          DOI  10.6039/j.issn.1001-0408.2022.22.11
          摘  要  目的  建立藤黄健骨胶囊质控成分的定量分析方法,并预测质控成分的潜在作用机制。方法  采用超高效液相色谱-四极
          杆-静电场轨道阱高分辨质谱(UHPLC-Q-Orbitrap HRMS)法对藤黄健骨胶囊中的7种质控成分进行定量分析;基于网络药理学方
          法构建“成分-靶点”网络,并进行京都基因和基因组数据库(KEGG)通路富集以及基因本体(GO)功能富集分析,挖掘潜在关键信
          号通路。结果  20批藤黄健骨胶囊中琥珀酸、金丝桃苷、没食子酸、山柰酚、柚皮苷、柚皮素、原儿茶酸的平均含量分别为520.92、
          67.67、129.48、4.74、397.45、5.66、376.62 μg/g。网络药理学结果显示,7 种质控成分的 62 个关键作用靶点基因包括 AKT1、TNF、
          VEGFA、MMP9、PTGS2等;主要富集于细胞因子受体相互作用、细胞核因子、肿瘤坏死因子、白细胞介素17、类风湿性关节炎、Toll
          样受体等信号通路,涉及炎症反应、信号转导、蛋白磷酸化等生物过程,胞质、包膜等细胞组分,以及酶活性、能量活性等分子功能。
          结论  所建UHPLC-Q-Orbitrap HRMS法可用于藤黄健骨胶囊质控成分的定量分析;其质控成分可能是通过AKT1、TNF、VEGFA等
          关键靶点,从而映射到类风湿性关节炎、Toll样受体等骨性疾病相关炎症通路,从而发挥治疗作用。
          关键词  藤黄健骨胶囊;质控成分;含量测定;网络药理学;机制

          Establishment  of  quantitative  analysis  method  and  prediction  of  potential  mechanism  for  quality  control
          components of Tenghuang jiangu capsules
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          ZHOU Lin ,WANG Xiaohui ,SUN Zhi ,XUE Lianping ,JIN Jianwen ,WU Jing ,LI Xiaojing ,ZHENG
          Tianyuan ,ZHANG Xiaojian(1.  Dept.  of  Pharmacy,  the  First  Affiliated  Hospital  of  Zhengzhou  University,
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          Zhengzhou  450052,  China;  2.  School  of  Minerals  Processing  and  Bioengineering,  Central  South  University,
          Changsha  410000,  China;  3.  Dept.  of  Ultrasound,  the  First  Affiliated  Hospital  of  Zhengzhou  University,
          Zhengzhou 450052, China; 4. Shaanxi Licai Pharmaceutical Co., Ltd., Shaanxi Xianyang 712000, China)
          ABSTRACT   OBJECTIVE  To  establish  a  quantitative  analysis  method  for  the  quality  control  components  in  Tenghuang  jiangu
          capsules,  and  predict  the  possible  action  mechanism  of  the  quality  control  components.  METHODS  Seven  key  quality  control
          components  in  Tenghuang  jiangu  capsules  were  quantitatively  analyzed  by  UHPLC-Q-Orbitrap  HRMS.  The “component-target”
          network  was  constructed  based  on  network  pharmacology,  and  the  Kyoto  Encyclopedia  of  Genes  and  Genomes (KEGG)  pathway
          enrichment  analysis  and  gene  ontology (GO)  function  enrichment  analysis  were  further  conducted  to  find  the  key  signaling
          pathways.  RESULTS  The  average  contents  of  succinic  acid,  hyperoside,  gallic  acid,  kaempferol,  naringin,  naringenin  and
          protocatechuic acid in 20 batches of Tenghuang jiangu capsules were 520.92, 67.67, 129.48, 4.74, 397.45, 5.66 and 376.62 μg/g,
          respectively. The results of network pharmacology showed that the 62 key target genes of the quality control components of the drug
          included AKT1,  TNF,  VEGFA,  MMP9,  PTGS2,  etc.  They  were  mainly  enriched  in  cytokine  receptor  interaction,  nuclear  factor,
          tumor  necrosis  factor,  interleukin  17,  rheumatoid  arthritis,  Toll-like  receptor  and  other  signal  pathways,  involving  inflammatory
          reaction,  signal  transduction,  protein  phosphorylation  and  other  biological  processes,  kytoplasm,  cell  membrane  and  other  cell
          components, as well as enzyme activity, energy activity and other molecular functions. CONCLUSIONS The established UHPLC-
          Q-Orbitrap HRMS method can be used for the quantitative analysis of the quality control components of Tenghuang jiangu capsule.
          Its  quality  control  components  may  be  mapped  to  inflammatory  pathways  related  to  bone  diseases  such  as  rheumatoid  arthritis  and
          Toll-like receptors through AKT1, TNF, VEGFA and other key targets, so as to play a therapeutic role.
                                                             KEYWORDS     Tenghuang  jiangu  capsule;  quality  control
             Δ 基金项目 河南省科技发展计划项目(No.212102311107)             components;  content  determination;  network  pharmacology;
             *第一作者 主管药师,博士研究生。研究方向:药物分析。                     mechanism
          E-mail:fcczhoul@zzu.edu.cn
             # 通信作者 主 任 药 师 。 研 究 方 向 :医 院 药 学 。 E-mail:
          zhangxiaojian_yxb@163.com


          中国药房  2022年第33卷第22期                                              China Pharmacy  2022 Vol. 33  No. 22    · 2743 ·
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