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采用超高效液相色谱- Q-Exactive Orbitrap 串联质谱联用网络药理学系统研究女贞子在大鼠血浆中的吸收成分及其代谢途径。

Systematic characterization of the absorbed components of Ligustri Lucidi Fructus and their metabolic pathways in rat plasma by ultra-high-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry combined with network pharmacology.

机构信息

Pharmaceutical department, College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, P. R. China.

Pharmaceutical department, College of Pharmacy, Dalian Medical University, Dalian, P. R. China.

出版信息

J Sep Sci. 2021 Dec;44(24):4343-4367. doi: 10.1002/jssc.202100484. Epub 2021 Nov 5.

Abstract

Ligustri Lucidi Fructus is a dried and mature fruit of Ligustrum lucidum Ait., which has the effects of nourishing liver and kidney. Herein, an accurate and sensitive method was established for the separation and identification of the absorbed constituents and metabolites of Ligustri Lucidi Fructus in rat plasma based on ultra-high-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry. A total of 73 prototype constituents and 148 metabolites were identified or characterized in administered plasma, and the possible metabolic pathways of constituents mainly involved hydroxylation, sulfation, demethylation, and glucuronidation. Besides, the network pharmacology was further investigated to illuminate its potential mechanism of treatment for liver injury by the biological targets regulating related pathways. Network pharmacological analysis showed that target components through 399 targets regulate 220 pathways. The docking results showed that 36 key target components were closely related to liver injury. Overall, the study clearly presented the metabolic processes of Ligustri Lucidi Fructus and gave a comprehensive metabolic profile of Ligustri Lucidi Fructus in vivo first. Combining with network pharmacology and molecular docking discovered potential drug targets and disclose the biological processes of Ligustri Lucidi Fructus, which will be a viable step toward uncovering the secret mask of study for traditional Chinese medicine.

摘要

女贞子为木樨科植物女贞 Ligustrum lucidum Ait. 的干燥成熟果实,具有滋补肝肾的功效。本研究采用超高效液相色谱-四级杆静电场轨道阱高分辨质谱联用技术建立了一种准确、灵敏的方法,用于分离和鉴定女贞子在大鼠血浆中的吸收成分和代谢物。在给予的血浆中鉴定或表征了 73 个原型成分和 148 个代谢物,成分的可能代谢途径主要涉及羟化、硫酸化、去甲基化和葡萄糖醛酸化。此外,还进一步进行了网络药理学研究,通过调节相关途径的生物靶标来阐明其治疗肝损伤的潜在机制。网络药理学分析表明,通过 399 个靶标调节 220 条通路的靶成分。对接结果表明,36 个关键靶成分与肝损伤密切相关。总之,该研究清楚地呈现了女贞子的代谢过程,并首次提供了女贞子在体内的全面代谢图谱。结合网络药理学和分子对接发现了潜在的药物靶点,并揭示了女贞子的生物学过程,这将是揭示中药研究秘密的可行步骤。

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