Hesperetin-Enhanced Metformin to Alleviate Cognitive Impairment via Gut-Brain Axis in Type 2 Diabetes Rats.

ABSTRACT: Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and cognitive decline. The use of metformin for treating cognitive impairment remains controversial. The present study found that hesperetin, a flavanone derived from citrus peel, enhanced metformin's efficacy in reducing blood sugar levels, improving insulin sensitivity, and ameliorating cognitive impairment in diabetic rats. Additionally, it reduced the required dosage of metformin to one-third of its conventional dose. Transcriptome analysis and 16S rRNA sequencing revealed that the activation of insulin and cyclic-adenosine monophosphate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathways benefited from

SUBMITTER: Zhang D 

PROVIDER: S-EPMC11900253 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature