摘要
目的根据中药质量标志物(Q-Marker)概念,基于指纹图谱、网络药理学和多指标定量技术筛选荷丹片治疗高脂血症的潜在Q-Marker。方法首先建立荷丹片高效液相色谱(HPLC)指纹图谱,并利用化学模式识别技术筛选影响荷丹片质量的差异性成分;继而采用网络药理学技术,预测差异性成分的潜在作用靶点及通路,并根据degree值筛选出荷丹片治疗高脂血症的潜在Q-Marker;最后采用超高效液相色谱(UHPLC)法进行多指标定量分析。结果建立了17批荷丹片样品的指纹图谱,共标定21个共有峰;化学模式识别结合对照品指认,共确定了10个影响荷丹片质量的关键差异性成分;网络药理学分析显示,上述10个差异性成分通过作用于Akt1、TNF、PPARG、MMP9、TP53、HMGCR等靶点,调控内分泌抵抗、胰岛素抵抗、脂质与动脉粥样硬化等信号通路发挥降脂作用,其中具有较大degree值的6种核心活性成分(番泻苷A、迷迭香酸、槲皮素-3-O-葡萄糖醛酸苷、金丝桃苷、补骨脂苷、荷叶碱)被最终确定为荷丹片的潜在Q-Marker。该6种成分在17批荷丹片样品中的含量范围分别为0.01~0.09、0.02~0.27、0.21~4.30、0.09~1.71、0.06~0.54、0.11~0.60 mg/片。结论所筛选出的6种化学成分(番泻苷A、迷迭香酸、槲皮素-3-O-葡萄糖醛酸苷、金丝桃苷、补骨脂苷、荷叶碱)符合中药质量标志物的配伍环境、有效性、专属性、可测性等原则,可作为荷丹片治疗高脂血症的潜在Q-Marker。
Objective Based on the concept of quality marker(Q-marker)in traditional Chinese medicine(TCM),the fingerprint,network pharmacology and multi-constituent quantification were used to screen the potential Q-Marker of Hedan Tablets(HDT)for the treatment of hyperlipidemia.Methods Firstly,the HPLC fingerprint of HDT was established and the differential markers were analyzed by chemical pattern recognition.Secondly,by using network pharmacology,the potential targets and pathways of HDT in treatment of hyperlipidemia were predicted,and the potential Q-Marker then screened out according to the degree value.Finally,a UHPLC-based multi-constituent quantification was established to determine the content of the predicted landmark components.Results The fingerprint was established and 21 common peaks were detected,from which 10 differential markers were selected by chemical pattern recognition and confirmed by reference substance chromatography.Utilizing network pharmacology analysis,the above 10 differential markers exert lipid-lowering effects by acting on Akt1,TNF,PPARG,MMP9,TP53,HMGCR and other targets to modulate the signaling pathways of endocrine resistance,insulin resistance,lipids and atherosclerosis.And then 6 core active ingredients,including sennoside A,rosmarinic acid,quercetin-3-O-glucuronide,hyperoside,psoralenoside and nuciferine were screened as the potential Q-Markers based on the degree value,with the content of 0.01~0.09,0.02~0.27,0.21~4.30,0.09~1.71,0.06~0.54,0.11~0.60 mg per tablet,respectively.Conclusion The above 6 core active ingredients were consistent with the screening principles of TCM Q-Markers,such as the compatibility environment,effectiveness,specificity and measurability,and could be used as potential Q-Markers for HDT in the treatment of hyperlipidemia.
作者
曹艺凡
夏林波
谢燕
李汉月
邹烨
邓仕任
CAO Yifan;XIA Linbo;XIE Yan;LI Hanyue;ZOU Ye;DENG Shiren(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116600,China)
出处
《药学研究》
2026年第2期121-129,140,共10页
Journal of Pharmaceutical Research
基金
辽宁省自然科学基金项目(No.20170540617)
辽宁中医药大学大学生创新创业训练计划项目(No.202310162003)。
关键词
荷丹片
高脂血症
质量标志物
网络药理学
化学模式识别
指纹图谱
多指标定量
Hedan Tablets
Hyperlipidemia
Quality markers
Network pharmacology
Chemical pattern recognition
Fingerprint
Multi-constituent quantification
