Study on the mechanism of American ginseng extract for treating type 2 diabetes mellitus based on metabolomics.

Study on the mechanism of American ginseng extract for treating type 2 diabetes mellitus based on metabolomics.
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基于代谢组学的西洋参提取物治疗2型糖尿病机制研究。

DOI:
10.3389/fphar.2022.960050
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发表时间:
2022
影响因子:
5.6
通讯作者:
Wu, Xiaohui
Wu, Xiaohui
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Tiantian;Wang, Dan;Zhou, Xinfeng;Song, Jiayin;Yang, Zijun;Shi, Chang;Li, Rongshan;Zhang, Yanwen;Zhang, Jun;Yan, Jiuxing;Zhu, Xuehui;Li, Ying;Gong, Min;Wang, Chongzhi;Yuan, Chunsu;Cui, Yan;Wu, Xiaohui

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西洋参提取物(AGE)是治疗2型糖尿病(T2 DM)的有效低毒佐剂。然而,AGE抗T2 DM的代谢机制仍不清楚。本研究建立了2型糖尿病大鼠模型,连续给药28天。收集其生物学(体重和血清生化指标)和病理(胰腺切片HE染色)信息,用于进一步的药效学评价。此外,采用基于超高效液-质联用的非靶向代谢组学方法,从所有大鼠的血清样本中筛选出潜在的生物标志物和相关的代谢途径。结果表明,大剂量AGE和二甲双胍治疗后,大鼠体重、空腹血糖(FBG)、空腹胰岛素(FINS)、血甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(ISI)明显改善,胰岛细胞受损程度明显改善。代谢组学分析确定了101个潜在的生物标志物,其中94个代谢物具有明显的回调作用。这些潜在的生物标志物主要集中在与氨基酸代谢和脂肪代谢相关的9条代谢途径中。进一步探讨了色氨酸代谢和谷胱甘肽代谢作为AGE和二甲双胍治疗T2 DM的不同代谢途径。进一步分析上述结果表明,AGE的抗T2 DM作用与炎症、氧化应激、内皮功能障碍、血脂异常、免疫反应、胰岛素抵抗、胰岛素分泌以及T2 DM相关并发症密切相关。本研究为系统探讨AGE抗T2 DM的作用机制提供了有力支持,为T2 DM的临床诊断提供了依据。
American ginseng extract (AGE) is an efficient and low-toxic adjuvant for type 2 diabetes mellitus (T2DM). However, the metabolic mechanisms of AGE against T2DM remain unknown. In this study, a rat model of T2DM was created and administered for 28 days. Their biological (body weight and serum biochemical indicators) and pathological (pancreatic sections stained with HE) information were collected for further pharmacodynamic evaluation. Moreover, an ultra-performance liquid chromatography–mass spectrometry–based (UHPLC–MS/MS–based) untargeted metabolomics method was used to identify potential biomarkers of serum samples from all rats and related metabolic pathways. The results indicated that body weight, fasting blood glucose (FBG), fasting blood insulin (FINS), blood triglyceride concentration (TG), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI), and impaired islet cells were significantly improved after the high dose of AGE (H_AGE) and metformin treatment. Metabolomics analysis identified 101 potential biomarkers among which 94 metabolites had an obvious callback. These potential biomarkers were mainly enriched in nine metabolic pathways linked to amino acid metabolism and lipid metabolism. Tryptophan metabolism and glutathione metabolism, as differential metabolic pathways between AGE and metformin for treating T2DM, were further explored. Further analysis of the aforementioned results suggested that the anti-T2DM effect of AGE was closely associated with inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, immune response, insulin resistance, insulin secretion, and T2DM-related complications. This study can provide powerful support for the systematic exploration of the mechanism of AGE against T2DM and a basis for the clinical diagnosis of T2DM.
DOI: 10.1093/ecam/nel026
发表时间: 2006-09
期刊: Evidence-based complementary and alternative medicine : eCAM
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