基于大鼠机体能量代谢生物标志物变化的黄芩药性研究

Study on the properties of baical skullcap root based on the change of biomarkers in rat's body energy metabolism

目的:运用代谢组学方法探究黄芩及其拆分组分对寒、热证模型大鼠能量代谢的影响,寻找潜在干预靶点及其代谢途径,通过整合分析探讨其作用机制并对各组分的药性进行归属,为黄芩合理用药及临床应用提供重要依据。方法:基于代谢组学角度对黄芩及其拆分组分进行药性归属,以及与能量代谢有关的药效学评价。采用Unify软件对各组分中化合物进行鉴定,并通过高效液相色谱法(HPLC)、超高压液相色谱-飞行时间质谱技术(UPLC-TOF-MS)与MarkerlynxTM软件进行互不交叉验证。通过UPLC-TOF-MS技术对黄芩干预的寒、热证大鼠尿液进行代谢组学研究。结果:代谢组学结果显示,寒证模型大鼠鉴定出2-氨基马来酸等10个与能量代谢相关的生物标志物。其中黄芩全成分可减慢基因转录进程和促进色酪氨酸代谢过程。黄芩多糖可抑制谷胱甘肽代谢、能量代谢及三羧酸循环。黄芩苷元作用不明显。黄芩苷类能够对能量代谢起到显著抑制作用。热证模型大鼠鉴定出色胺等10个与能量代谢相关的生物标志物。其中黄芩全成分可减慢核酸代谢和细胞代谢过程;黄芩多糖除了与全成分有相似的作用外,还能减慢葡萄糖代谢;黄芩苷元能抑制核酸代谢与糖代谢;黄芩苷类能够抑制核酸代谢。结论:黄芩对寒、热证模型大鼠能量代谢作用呈现抑制的趋势,并且干预靶点不同,证明在其4段不同的药效物质基础组分中,全成分、苷类、苷元、多糖均为寒性。

Objective： Metabolomics were utilized to investigate the effect of baical skullcap root（BSR） and its split components on the energy metabolism of cold and heat syndrome model rats and to explore the potential targets and metabolic pathways. The significant foundation of SBS＇s rational administration and clinical application was obtained via comprehensively analyzing and exploring the mechanism of action as well as assigning drug property categorization of each component. Methods： Based on the metabolomics, pharmacodynamics profile of BSR and its split components were studied involved with drug property attribution and energy metabolism. BSR＇s compounds were identified by Unify software, HPLC, UPLC-TOF-MS and MarkerlynxTM software. The UPLC-TOF-MS technique was used to study the urine of the cold and heat syndrome model rats treated with SBS. Results： The result of metabonomics showed that, the urine profile of cold syndrome model rats changed significantly following intervention of BSR. Ten biomarkers associated with energy metabolism including 2-Aminomuconic acid were identified. The total composition of BSR could slow the process of genetic transcription and promote the tryptophan metabolism process. Polysaccharide of BSR could decrease the levels of energy metabolism, glutathione metabolism and tricarboxylic acid cycle. The action of aglycone was not obvious. The glycosides had inhibitory effect on the energy metabolism. 10 biomarkers associated with energy metabolism including tryptamine were identified. The total composition of BSR could slow down the process of genetic metabolism and cell metabolism. Polysaccharide could decrease glucose metabolism. Aglycone could inhibit nucleic acid metabolism, glucose metabolism and inhibit energy metabolism. Glycosides could significantly inhibit the nucleic acid metabolism. Conclusion： BSR has different effects and interfere targets on the energy metabolism of the cold and heat syndrome model rats. It is proved that the total BSR, glycosides, aglycone and polysaccharide are cold.