T2DM患者的代谢组学与黄柏-川贝母对小鼠抗糖尿病作用的关系

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2024-11-20 DOI:10.1016/j.jep.2024.119129

Jia-Lin Yu , Zhen-Yang Zhang , Sheng-Ping Liu , Hong-Ping Long , Ting-Ting Wang , Feng-Qing Huang , Jia Guo , Wei-Long Xu , Fei Li

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引用次数: 0

摘要

民族药理学意义：2 型糖尿病（T2DM）对公众健康构成重大威胁。在传统中医中，黄柏（Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma，PCC/AR）这对草药长期以来一直被用于治疗 T2DM，但其具体的抗糖尿病机制仍不清楚：本研究旨在通过临床代谢组学和体内外实验，阐明 T2DM 患者的代谢组学与 PCC/AR 草药对小鼠抗糖尿病作用之间的关系：本研究通过高脂喂养（HFD）和注射链脲佐菌素（STZ）建立了T2DM小鼠模型。评估了 PCC/AR 对血糖、脂代谢和炎症指标的影响。对 T2DM 患者进行了高效液相色谱-质谱（HPLC-MS）代谢组学分析：结果：血清代谢组学分析发现，T2DM 患者体内与不饱和脂肪酸生物合成和嘌呤代谢相关的代谢物发生了显著变化，2-羟基戊酸（2HB）水平升高。在 T2DM 小鼠中，PCC/AR 干预可使 FBG、GHbA1c、TC、TG、LDL-C、HDL-C、TNF-α 和 IL-1β 水平正常化，同时改善 T2DM 小鼠的胰岛素敏感性和胰岛 β 细胞功能。值得注意的是，PCC/AR 降低了葡萄糖生成和脂肪酸合成过程中的关键酶 PEPCK 和 ACC1：结论：PCC/AR 草药配对通过抑制 ACC1 来调节 2HB，从而减少 FFA 和 TG 的合成，对 T2DM 小鼠具有抗糖尿病作用。此外，PCC/AR 还可能通过调节葡萄糖和脂质代谢以及减少炎症来发挥其作用。这些结果支持进一步研究 PCC/AR 药草配对作为治疗 T2DM 的辅助疗法。

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Relationship between metabolomics of T2DM patients and the anti-diabetic effects of Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma herb pair in mice

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Relationship between metabolomics of T2DM patients and the anti-diabetic effects of Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma herb pair in mice

Ethnopharmacological relevance

Type 2 diabetes mellitus (T2DM) poses significant threats to public health. In Traditional Chinese Medicine (TCM), the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma (PCC/AR) herb pair has long been used for T2DM treatment, although its specific anti-diabetic mechanisms remain unclear.

Aim of the study

This study aimed to elucidate the relationship between metabolomics of T2DM patients and the anti-diabetic effects of PCC/AR herb pair in mice through clinical metabolomics and both in vitro and in vivo experiments.

Materials and methods

In this study, a T2DM mouse model was established via high-fat feeding (HFD) and streptozotocin (STZ) injection. The effects of PCC/AR on blood glucose, lipid metabolism, and inflammatory markers were evaluated. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed for metabolomics analysis of T2DM patients.

Results

Serum metabolomics analysis identified significant alterations in metabolites linked to the biosynthesis of unsaturated fatty acids and purine metabolism in T2DM patients, with elevated 2-hydroxyvaleric acid (2HB) levels. In T2DM mice, PCC/AR intervention normalized FBG, GHbA1c, TC, TG, LDL-C, HDL-C, TNF-α and IL-1β levels, while improving insulin sensitivity and pancreatic β-cell function in T2DM mice. Notably, PCC/AR reduced key enzymes in gluconeogenesis and fatty acid synthesis, PEPCK and ACC1.

Conclusion

PCC/AR herb pair exerts an anti-diabetes effect in T2DM mice by regulating 2HB through ACC1 inhibition, thereby reducing FFA and TG synthesis. Additionally, PCC/AR may also exert its effects by modulating glucose and lipid metabolism and reducing inflammation. These results support further investigation into the PCC/AR herb pair as a complementary therapy for T2DM.

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.