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揭示冬凌草甲素在链脲佐菌素诱导的糖尿病大鼠中的抗糖尿病作用的药理学机制:血清代谢组学的综合分析。

Unveiling the Pharmacological Mechanisms of Davidiin's Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome.

机构信息

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.

Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.

出版信息

Drug Des Devel Ther. 2024 Jun 5;18:1981-1996. doi: 10.2147/DDDT.S459931. eCollection 2024.

Abstract

BACKGROUND

Buch.-Ham. ex D. Don (), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties.

MATERIALS AND METHODS

Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS.

RESULTS

Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins.

CONCLUSION

Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin's action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.

摘要

背景

山麦冬(),苗医常用草药,以清心功效闻名。其中的主要生物活性成分(约 1%)大卫碱,已被用于治疗多种疾病,包括糖尿病。鉴于其广泛的作用和糖尿病涉及的多种生物分子途径,研究大卫碱如何与这些途径相互作用以更好地了解其抗糖尿病特性至关重要。

材料和方法

采用高脂饮食和腹腔注射链脲佐菌素(STZ,35mg/kg)诱导糖尿病大鼠。其中 24 只血糖≥11.1mmol/L 且空腹血糖≥7.0mmol/L 的大鼠被分为 3 个实验组,分别给予二甲双胍(灌胃,140mg/kg)或大卫碱(灌胃,90mg/kg)治疗 4 周。治疗结束后,测量体重、血糖水平,并采用 UPLC-QTOF-MS 进行非靶向代谢组学分析。

结果

大卫碱可有效降低血糖水平,从 30.2±2.6mmol/L 降至 25.1±2.4mmol/L(P<0.05),疗效优于二甲双胍(血糖水平降至 26.5±2.6mmol/L)。血清代谢组学的主要结果是脂质和类脂分子谱的显著变化。首先,大卫碱可能通过增加磷脂酰肌醇和神经鞘氨醇-1-磷酸水平影响磷脂代谢。其次,大卫碱可能通过降低甘氨胆酸和甘氨鹅脱氧胆酸水平影响胆固醇代谢。最后,大卫碱可能通过增加海鞘素 B3 水平和降低前列腺素水平影响甾体激素代谢。

结论

本研究表明,大卫碱通过调节多种与脂质相关的代谢途径发挥其抗糖尿病作用。这些发现提供了大卫碱作用机制的首个详细代谢谱,为中药治疗糖尿病领域提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f77/11162635/11c4576a1e85/DDDT-18-1981-g0001.jpg

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