UPLC-Q/TOF-MS-Based Serum Metabolomics Reveals the Potential Antihyperglycemic Mechanisms of Polygonatum sibiricum in KK/Upj-Ay Type 2 Diabetic Mice

IF 1.7 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Biomedical Chromatography Pub Date : 2025-07-29 DOI:10.1002/bmc.70177

Hao Li, Shuhan Tang, Jinyue Huang, Yidan Sun, Yaqi Xu, Yige Wang, XinTong Li, Minyue Zhang, Rong Ma, Xianna Li, Hongying Xu, Hailong Zhang, Zhigang Wang

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Abstract

Polygonatum sibiricum (PS) is a traditional Chinese medicinal herb used as both food and medicinal material. PS is reportedly significantly effective in the treatment of type 2 diabetes mellitus (T2DM) in clinic. However, its pharmacological mechanism and endogenous antihyperglycemic markers remain unknown. This study investigated PS effects in KK/Upj-Ay 2 diabetic mice and revealed its potential antihyperglycemic mechanisms. Nontargeted serum metabolomics and pathophysiological detection characterized differentially abundant metabolites and determined changes in metabolic pathways. Fasting blood glucose decreased, while serum total cholesterol (TC), tumor necrosis factor-α (TNF-α), triglyceride (TG), and whole blood hemoglobin A1c (HbA1c) levels in kidney tissue homogenates were restored to different degrees following administration with PS. Observation of hematoxylin–eosin (HE) staining of the kidney and pancreas, periodic acid-Schiff (PAS) staining of the kidney, and immunohistochemistry of pancreatic insulin revealed that PS could reduce dysfunction in KK/Upj-A^y 2 diabetic mice. Nontargeted serum metabolomics identified 37 T2DM biomarkers, 27 of which were significantly recovered by high-dose PS. Further pathway analysis revealed 11 key metabolic pathways involved in PS-mediated effects. These pathways regulate inflammation, lipid accumulation, oxidative stress, and insulin resistance, elucidating multitarget mechanisms by which PS ameliorates metabolic disturbances and exerts antihyperglycemic effects in KK/Upj-A^y type 2 diabetic mice.

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基于UPLC-Q/ tof - ms的血清代谢组学揭示了黄精对KK/Upj-Ay 2型糖尿病小鼠的潜在降糖机制

黄精（Polygonatum sibiricum， PS）是一种既可食用又可药用的传统中草药。据报道，PS在临床上治疗2型糖尿病（T2DM）有显著效果。然而，其药理机制和内源性抗高血糖标志物尚不清楚。本研究探讨了PS对KK/ upj - ay2型糖尿病小鼠的作用，并揭示了其潜在的降糖机制。非靶向血清代谢组学和病理生理检测表征了代谢物的差异丰富，并确定了代谢途径的变化。给药后，空腹血糖降低，血清总胆固醇（TC）、肿瘤坏死因子-α (TNF-α)、甘油三酯（TG）、全血血红蛋白A1c （HbA1c）水平均有不同程度恢复。胰岛胰岛素免疫组化结果显示，PS可减轻KK/ upj - ay2型糖尿病小鼠的功能障碍。非靶向血清代谢组学鉴定出37种T2DM生物标志物，其中27种通过高剂量PS显著恢复。进一步的途径分析揭示了11种参与PS介导作用的关键代谢途径。这些通路调节炎症、脂质积累、氧化应激和胰岛素抵抗，阐明了PS在KK/Upj-Ay 2型糖尿病小鼠中改善代谢紊乱和发挥抗高血糖作用的多靶点机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedical Chromatography 生物-分析化学

CiteScore

3.60

自引率

5.60%

发文量

268

审稿时长

2.3 months

期刊介绍： Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.