天然产物研究与开发 ›› 2026, Vol. 38 ›› Issue (8): 1777-1789.doi: 10.16333/j.1001-6880.2026.8.016 cstr: 32307.14.1001-6880.2026.8.016

• 数据研究 • 上一篇    下一篇

基于网络药理学和非靶向代谢组学探讨白术-苍术改善ob/ob小鼠肥胖的作用机制

李  静1,3,许宗颖1,3,徐进文1,3,骆欢欢1,2,3*   

  1. 1广州中医药大学 中医证候全国重点实验室,广州 510006;2中医药广东省实验室,横琴 519031;3广州中医药大学中西医结合基础研究中心,广州 510006
  • 出版日期:2026-08-27 发布日期:2026-08-26
  • 基金资助:
    国家自然科学基金(82174244,81774107);院校共建重点项目(GZYZS2024U03)

Mechanism of Atractylodis Macrocephalae Rhizoma-Atractylodis Rhizoma in improving obesity of ob/ob mice based on network pharmacology and untargeted metabolomics

LI Jing1,3,XU Zong-ying1,3,XU Jin-wen1,3,LUO Huan-huan1,2,3*   

  1. 1State Key Laboratory of Traditional Chinese Medicine Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510006,China; 2 Chinese Medicine Guangdong Laboratory,Hengqin 519031,China;3Research Centre of Basic Integrative Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China
  • Online:2026-08-27 Published:2026-08-26

摘要:

基于网络药理学和非靶向代谢组学,探讨白术-苍术(Atractylodis Macrocephalae Rhizoma-Atractylodis Rhizoma,AM-AL)药对改善肥胖的作用机制。采用ob/ob肥胖小鼠模型,Micro CT分析皮下脂肪(inguinal white adipose tissue,iWAT)和附睾脂肪(epididymal white adipose tissue,eWAT)体积;Masson染色法观察eWAT病理变化;ELISA检测eWAT中白细胞介素-6(interleukin 6,IL-6)、IL-17、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、丙二醛(malondialdehyde,MDA)含量。采用Q-Orbitrap高分辨液质联用技术对AM-AL入血成分进行定性分析。网络药理学技术筛选入血成分与疾病交集靶点。非靶向代谢组学技术筛选eWAT中差异代谢物及相关代谢通路后,联合网络药理学,构建“代谢物-反应-酶-基因”网络进行联合分析。动物实验结果表明,AM-AL-H能降低小鼠体重和日均进食量;降低iWAT和eWAT的体积;改善炎症和氧化应激水平。Q-Orbitrap鉴定AM-AL入血成分中有49个化合物。网络药理学结果显示,丝氨酸/苏氨酸激酶1(AKT serine/threonine kinase 1,AKT1)为核心靶点,主要涉及代谢通路、脂质与动脉粥样硬化等。非靶向代谢组学显示,AM-AL对药显著回调了20个差异代谢物,整合分析结果显示,甘油磷脂代谢可能是AM-AL入血成分发挥抗肥胖作用的关键通路。本实验初步阐明了AM-AL改善肥胖的作用机制,为其临床应用及后续研究提供了科学依据。

关键词: 白术-苍术, 肥胖, Q-Orbitrap高分辨液质联用, 网络药理学, 非靶向代谢组学

Abstract:

Based on network pharmacology and untargeted metabolomics,the mechanism of Atractylodis Macrocephalae Rhizoma-Atractylodis Rhizoma (AM-AL) herb pair improving obesity was explored.The ob/ob mice model of obesity was used.Micro CT was employed to analyze the volumes of inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT).Masson staining was used to observe the pathological changes of eWAT.ELISA was performed to detect the levels of interleukin-6 (IL-6),IL-17,tumor necrosis factor-α (TNF-α),and malondialdehyde (MDA) in eWAT.Q-Orbitrap high-resolution liquid chromatography-mass spectrometry was used to qualitatively analyze the absorbed components of AM-AL in serum.Network pharmacology technology was used to screene core targets between absorbed components and diseases.Untargeted metabolomics was used to screene differential metabolites of eWAT,and related metabolic pathways.Combined with network pharmacology,a "metabolite-reaction-enzyme-gene" network was constructed for joint analysis.The animal experiment results showed that the high-dose AM-AL group could reduce the body weight and daily food intake of mice;reduce the volume of iWAT and eWAT;and improve the levels of inflammation and oxidative stress.Q-Orbitrap identified 49 compounds in serum.Network pharmacology results showed that AKT serine/threonine kinase 1 (AKT1) was the core target,mainly involving metabolic pathways,lipids and atherosclerosis,and so on.Untargeted metabolomics showed that AM-AL significantly regulated 20 differential metabolites.The integrated analysis results indicated that glycerophospholipid metabolism might be the key pathway for the anti-obesity effect of AM-AL.This experiment initially clarified the mechanism of AM-AL in improving obesity,providing a scientific basis for its clinical application and subsequent research.

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中图分类号:  R285