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基于血清药物化学和网络药理学对方剂防己黄芪汤作用机制及有效成分的综合研究

Comprehensive investigation of mechanism and effective ingredients of Fangji Huangqi Tang by serum pharmacochemistry and network pharmacology.

作者信息

Yang Liu, Li Aiping, Chen Meng, Yan Yan, Liu Yuetao, Li Ke, Jia Jinping, Qin Xuemei

机构信息

Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, China.

College of Chemistry and Chemical Engineering of Shanxi University, Taiyuan, China.

出版信息

Biomed Chromatogr. 2020 Apr;34(4):e4785. doi: 10.1002/bmc.4785. Epub 2020 Jan 21.

Abstract

Fangji Huangqi Tang (FHT), has been reported to show effects on nephrotic syndrome, but its mechanism of action and bioactive components have not yet been determined. In this study, a method using UPLC-HRMS/MS was established for the detection and identification of the chemical constituents and metabolites absorbed into the blood. Absorbed components in serum were then used for the network pharmacology analysis to deduce the mechanism and effective components. A total of 86 compounds were identified or tentatively characterized. Based on the same instrumental conditions, 85 compounds were found in rat serum after oral administration of FHT, including 22 prototypes and 63 metabolites. Network pharmacology analysis showed that absorbed components, such as (3R)-2',3',4',7-tetrahydroxyisoflavan, astrapterocarpan, cycloastragenol, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, astragaloside IV, astrapterocarpan glucoside and glycyrrhetinic acid, could be responsible for the pharmacological activity of nephrotic syndrome by regulating the VEGF signaling pathway, focal adhesion and MAPK signaling pathway. Furthermore, the pathway-target network showed that the MAPK1, AKT2 and CDC42 were involved in the signal pathways above. This study provides a scientific basis for the mechanism and effective ingredients of FHT.

摘要

防己黄芪汤(FHT)已被报道对肾病综合征有疗效,但其作用机制和生物活性成分尚未确定。在本研究中,建立了一种使用超高效液相色谱-高分辨质谱/质谱(UPLC-HRMS/MS)的方法来检测和鉴定吸收入血的化学成分和代谢产物。然后将血清中的吸收成分用于网络药理学分析,以推断其作用机制和有效成分。共鉴定或初步表征了86种化合物。基于相同的仪器条件,在口服FHT后的大鼠血清中发现了85种化合物,包括22种原型化合物和63种代谢产物。网络药理学分析表明,吸收成分,如(3R)-2',3',4',7-四羟基异黄酮、紫穗槐二氢黄酮、环黄芪醇、7,2'-二羟基-3',4'-二甲氧基异黄酮、黄芪甲苷、紫穗槐二氢黄酮葡萄糖苷和甘草次酸,可能通过调节血管内皮生长因子(VEGF)信号通路、粘着斑和丝裂原活化蛋白激酶(MAPK)信号通路来发挥肾病综合征的药理活性。此外,通路-靶点网络显示,丝裂原活化蛋白激酶1(MAPK1)、蛋白激酶B2(AKT2)和细胞分裂周期蛋白42(CDC42)参与了上述信号通路。本研究为防己黄芪汤的作用机制和有效成分提供了科学依据。

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