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

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

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.

Keywords: Camellia oleifera flower; Total flavonoids; Type 2 diabetes; p53 signaling pathway.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Camellia* / chemistry
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Type 2* / drug therapy
  • Flavonoids* / isolation & purification
  • Flavonoids* / pharmacology
  • Flowers* / chemistry
  • Glycoside Hydrolase Inhibitors / isolation & purification
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Hypoglycemic Agents* / isolation & purification
  • Hypoglycemic Agents* / pharmacology
  • Insulin Resistance
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Flavonoids
  • Tumor Suppressor Protein p53
  • Hypoglycemic Agents
  • Glycoside Hydrolase Inhibitors
  • Blood Glucose
  • Trp53 protein, mouse