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油茶花花中类黄酮通过调节 p53 通路改善 2 型糖尿病。

Flavonoids from Camellia oleifera flower ameliorate type 2 diabetes mellitus by regulating the p53 pathway.

机构信息

Institutes of Natural Products and Human Health, Zhejiang University, Hangzhou, China.

College of Chemistry, Zhejiang University, Hangzhou, China.

出版信息

Fitoterapia. 2024 Dec;179:106267. doi: 10.1016/j.fitote.2024.106267. Epub 2024 Oct 18.

DOI:10.1016/j.fitote.2024.106267
PMID:39428078
Abstract

BACKGROUND

Camellia oleifera flower (COF) is rich in flavonoids and polyphenols, strongly preventing postprandial hyperglycemia and improving diabetes. However, research on the effective ingredients in COF extracts that have hypoglycemic effects is limited, and the mechanism by which COF extracts improve liver insulin resistance and glucose and lipid metabolism still needs to be clarified, requiring further investigation.

AIM

To systematically clarify the role of COF extracts in improving insulin resistance in diabetes mice and to explore their key targets and mechanisms in anti-type 2 diabetes (T2DM).

MATERIALS AND METHODS

Ultrafiltration combined with liquid chromatography-mass spectrometry (UPLC-Q-MS) was used to analyze α-glucosidase inhibitors in COF extracts qualitatively. Blood glucose, lipid, oxidative stress, and liver function indicators were detected in the db/db type 2 diabetes mouse model. Then, RNA-seq was used to identify differentially expressed mRNAs (DEGs) in the liver, screen for key genes and metabolic pathways, and validate the results' accuracy through qPCR experiments.

RESULTS

17 α-glucosidase inhibitors were identified as flavonoids from COF. Through db/db type 2 diabetes mouse model, it was indicated that COF could significantly improve symptoms of hyperglycemia and hyperlipidemia, alleviate oxidative stress, and protect liver and pancreatic tissues by regulating key differential genes expressed, including Nek2, Cdk1, Ccnb1, and Ccnb2 via the p53 signaling pathway and ameliorate the insulin resistance effect.

CONCLUSION

This study demonstrated the anti-diabetic effect of COF, explored its potential hypoglycemic target, and provided data support for future T2DM prevention and drug treatment.

摘要

背景

山茶花(COF)富含黄酮类和多酚类物质,能有效预防餐后高血糖,改善糖尿病。然而,关于 COF 提取物中具有降血糖作用的有效成分的研究有限,COF 提取物改善肝脏胰岛素抵抗和糖脂代谢的机制仍需阐明,需要进一步研究。

目的

系统阐明 COF 提取物在改善糖尿病小鼠胰岛素抵抗中的作用,并探讨其在抗 2 型糖尿病(T2DM)中的关键靶点和机制。

材料和方法

采用超滤结合液质联用(UPLC-Q-MS)技术对 COF 提取物中的α-葡萄糖苷酶抑制剂进行定性分析。在 db/db 型 2 型糖尿病小鼠模型中检测血糖、血脂、氧化应激和肝功能指标。然后,通过 RNA-seq 技术鉴定肝脏中差异表达的 mRNAs(DEGs),筛选关键基因和代谢通路,并通过 qPCR 实验验证结果的准确性。

结果

从 COF 中鉴定出 17 种α-葡萄糖苷酶抑制剂,均为黄酮类物质。通过 db/db 型 2 型糖尿病小鼠模型表明,COF 可通过调节关键差异表达基因,包括 Nek2、Cdk1、Ccnb1 和 Ccnb2,通过 p53 信号通路改善胰岛素抵抗作用,显著改善高血糖和高血脂症状,减轻氧化应激,保护肝脏和胰腺组织。

结论

本研究证实了 COF 的抗糖尿病作用,探讨了其潜在的降血糖靶点,为未来 T2DM 的预防和药物治疗提供了数据支持。

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