Microbiome–metabolomics analysis reveals the potential effect of verbascoside in alleviating cognitive impairment in db/db mice
- 16 March 2023
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Food & Function
- Vol. 14 (8), 3488-3508
- https://doi.org/10.1039/d2fo03110h
Abstract
Cognitive impairment is the main central nervous system complication of diabetes, affecting the quality of life of patients. Herba Cistanche is a homologous plant widely used as a health food and therapeutic drug. Verbascoside, a signature component of Herba Cistanche, has anti-diabetic and neuroprotective effects. However, it is quickly metabolized by the gut microbiota, and the mechanism of its neuroprotection and improvement of learning and memory remains unclear. We investigated the effectiveness and potential mechanisms of verbascoside on cognitive dysfunction in db/db mice using a 16S rRNA microbiome and serum metabolomics approach. We found that 12-week treatment with verbascoside significantly inhibited insulin resistance, reduced blood glucose and lipids, and improved cognitive deficits. In addition, verbascoside increased the gut microbiota diversity, improved intestinal dysbiosis, attenuated intestinal barrier disruption, reduced the levels of inflammatory factors, regulated the expression of the metabolites associated with cognitive function, and enhanced the central insulin sensitivity and hippocampal synaptogenesis signaling. We revealed that verbascoside induced the enrichment of Alistipes, Roseburia, and Intestinimonas in the gut, suppressed the abundance of Escherichia–Shigella, increased the serum levels of gamma-aminobutyric acid, L-glutamic acid, and L-lysine, and decreased taurine expression. Finally, a strong association between gut microbes, serum metabolites, and cognitive performance affected by verbascoside was observed. Our research suggests that alterations in gut microbes/metabolites are involved in the development of diabetic cognitive dysfunction, which is alleviated by verbascoside in the db/db mice through restructuring the gut microbiota composition, ameliorating diabetic metabolic disorders, and attenuating pathological brain damage.Funding Information
- National Natural Science Foundation of China (81860735)
- Science and Technology Department of Xinjiang Uyghur Autonomous Region (2021D01D11, 2022D01D14)
This publication has 86 references indexed in Scilit:
- Phenolic Antioxidants Isolated from the Flowers of Osmanthus fragransMolecules, 2012
- Risk of Hypoglycemia in Older Veterans with Dementia and Cognitive Impairment: Implications for Practice and PolicyJournal of the American Geriatrics Society, 2011
- Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic CooperationCell Metabolism, 2011
- Cognitive and Emotional Alterations Are Related to Hippocampal Inflammation in a Mouse Model of Metabolic SyndromePLOS ONE, 2011
- Normal gut microbiota modulates brain development and behaviorProceedings of the National Academy of Sciences of the United States of America, 2011
- Analysis of chemical constituents in Cistanche speciesJournal of Chromatography A, 2009
- Dose translation from animal to human studies revisitedThe FASEB Journal, 2007
- Synapse-specific regulation of AMPA receptor function by PSD-95Proceedings of the National Academy of Sciences of the United States of America, 2006
- The glutamate/GABA‐glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transferJournal of Neurochemistry, 2006
- Hippocampal long-term potentiation and spatial learning in the rat: effects of GABAB receptor blockadeNeuroscience, 1996