Screening the components in multi-biological samples and the comparative pharmacokinetic study in healthy and depression model rats of Suan-Zao-Ren decoction combined with a network pharmacology
Screening the components in multi-biological samples and the comparative pharmacokinetic study in healthy and depression model rats of Suan-Zao-Ren decoction combined with a network pharmacology
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DOI：
10.1016/j.jep.2023.117360
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发表时间：
2023-10-29
影响因子：
5.4
通讯作者：
He，Bosai
中科院分区：
文献类型：
--
作者：
Du，Yiyang;Wang，Jiahong;He，Bosai
民族药理学相关性酸枣仁汤（SZRD）是一个经典的传统中药方剂，常用于治疗失眠，抑郁症和其他神经系统疾病。本研究的目的本研究旨在探讨代谢谱在多个-生物样品和药代动力学机制之间的健康和抑郁症模型大鼠结合网络药理学方法后，SZRD。材料和方法本研究首次采用超高效液相色谱-Q-Exactive Orbitrap质谱联用技术研究了抑郁症大鼠和健康大鼠血浆、脑、尿和粪便中SZRD的原型成分和代谢产物。并对可能的代谢途径进行了推测。然后对模型大鼠血浆中的成分进行了网络药理学研究。根据网络药理学筛选出的上述组分，并结合其他已报道的代表性活性成分，建立了同时测定芒果苷、刺果苷、阿魏酸、甘草苷、芒柄花素的比较药代动力学研究。木兰花碱和异甘草苷的差异。结果在健康大鼠体内共鉴定出115个活性成分，在模型大鼠体内共鉴定出101个活性成分。还区分了血浆、脑、尿液和粪便中的原型组分和代谢产物。主要代谢途径包括脱氢、氧化、羟基化、乙醛结合、谷胱甘肽结合等I相和II相代谢反应，为进一步研究SZRD抗抑郁药代动力学和药理作用奠定了基础。然后，根据网络药理学研究的程度值，预测了10个组分和10个核心靶点，涉及神经活性配体-受体相互作用、环磷酸腺苷（cAMP）信号通路、多巴胺能突触、磷脂酰肌醇-3激酶（PI 3 K）-Akt信号通路等关键通路。建立的药代动力学方法成功地应用于正常大鼠和抑郁症大鼠口服SZRD后血浆中这7种活性成分的药代动力学行为的比较。结果表明，除木兰花碱外，各组分在健康大鼠和抑郁大鼠体内的药动学参数均不同。分子对接分析也表明，药代动力学活性成分能与网络药理学研究的关键靶点紧密结合。结论本研究为深入研究SZRD治疗抑郁症的作用机制提供了重要信息。
Ethnopharmacological relevanceSuanzaoren Decoction (SZRD) is a classic traditional Chinese prescription, which has been commonly used for treating insomnia, depression and other nerve system diseases for a long time.Aim of this studyThe present study aimed to explore the metabolic profiles in multi-biological samples and pharmacokinetic mechanism between healthy and depression model rats combined with a network pharmacology approach after administration of SZRD.Materials and methodsIn our study, an ultra-high performance liquid chromatography (UPLC)-Q-Exactive Orbitrap Mass Spectrometry method was firstly used to study the prototype components and metabolites of SZRD in plasma, brain, urine, and feces between healthy and depressed rats. The possible metabolic pathways were also speculated. Then a network pharmacological study was conducted on the components in the plasma of model rats. According to the above components screened by network pharmacology and the other reported representative active components, the comparative pharmacokinetic study was established for the simultaneous determination of mangiferin, spinosin, ferulic acid, liquiritin, formononetin. magnoflorine and isoliquiritin between healthy and depression model rats. Finally, molecular docking was used to validate the binding affinity between key potential targets and active components in pharmacokinetics.ResultsA total of 115 components were identified in healthy rats, and 101 components were identified in model rats. The prototype components and metabolites in plasma, brain, urine, and feces were also distinguished. The main metabolic pathways included phase I and phase II metabolic reactions, such as dehydrogenation, oxidation, hydroxylation, gluconaldehyde conjugation, glutathione conjugation and so on. These results provided a basis for the further study of antidepressive pharmacokinetic and pharmacological action in SZRD. Then, according to the degree value of network pharmacological study, it was predicted that 10 components and 10 core targets, which involved in the critical pathways such as neuroactive ligand-receptor interaction, cyclic adenosine monophosphate (cAMP) signaling pathway, serotonergic synapse, phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway, etc. Finally, the established pharmacokinetic method was successfully applied to compare the pharmacokinetic behavior of these 7 active components in plasma of healthy and depressed rats after oral administration of SZRD. It showed that except magnoflorine, the pharmacokinetic parameters of each component were different between healthy and depressed rats. Molecular docking analysis also indicated that the active compounds in pharmacokinetics could bind tightly to the key targets of network pharmacological study.ConclusionThis study may provide important information for studying the action mechanism of SZRD in treating depression.