Hypoglycemic Effect of Nobiletin via Regulation of Islet β-Cell Mitophagy and Gut Microbiota Homeostasis in Streptozocin-Challenged Mice.
Sijie YuanZichong YeYe LiJiaxuan ZouMengting WuKe WangWenzhen LiaoJie ShenPublished in: Journal of agricultural and food chemistry (2022)
Nobiletin is a natural nutrient (or polymethoxyflavonoid) in orange peels exerting a preventive effect against metabolic diseases. However, there are very few reports on the hypoglycemic effect of nobiletin. In the present study, the hypoglycemic effect of nobiletin was investigated using NIT-1 cells and streptozocin (STZ)-challenged mouse models. Our results indicated that nobiletin could significantly suppress the high blood glucose in STZ-challenged mice. In addition, nobiletin could effectively activate the mitophagy and inhibit the inflammatory pathways in NIT-1 cells. The mitochondria membrane potential dysbiosis induced by glucotoxicity in NIT-1 cells was restored after treatment by nobiletin. Further investigation revealed that the hypoglycemic effect of nobiletin was mainly through regulation of gut microbiota dysbiosis, activation of mitophagy flux, inhibition of inflammasome expression, and restoration of islet morphological destruction in the pancreas of STZ-challenged mice. Our study revealed that nobiletin could be used as a functional food or drug candidate for the treatment of diabetes.
Keyphrases
- induced apoptosis
- blood glucose
- cell cycle arrest
- single cell
- oxidative stress
- type diabetes
- diabetic rats
- poor prognosis
- endoplasmic reticulum stress
- mouse model
- high fat diet induced
- signaling pathway
- emergency department
- nlrp inflammasome
- stem cells
- mass spectrometry
- bone marrow
- human health
- high resolution
- pi k akt
- reactive oxygen species
- adverse drug
- replacement therapy