ArticleDisease models & mechanisms2022
Xanthohumol improves cognition in farnesoid X receptor-deficient mice on a high-fat diet.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Xanthohumol: Mechanistic Actions and Emerging Evidence as a Multi-Target Natural Nutraceutical.Nutrients · 2026Review
- Xanthohumol and its non-estrogenic derivatives link to the gut-liver-brain axis to improve cognition in mice with diet-induced obesity.Frontiers in physiology · 2026Article
- Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework.Frontiers in aging neuroscience · 2026Review
- Effects of a high-fat diet on cognition and brain distribution of intranasal insulin in E3 and E4 male and female mice.Scientific reports · 2024Article
- Sex matters in preclinical research.Disease models & mechanisms · 2024Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Xanthohumol (XN) improves cognition of wild-type rodents on a high-fat diet (HFD). Bile acids and ceramide levels in the liver and hippocampus might be linked to these effects. XN modulates activity of the nuclear farnesoid X receptor (FXR; also known as NR1H4), the primary receptor for bile acids. To determine the role of FXR in the liver and intestine in mediating the effects of XN on cognitive performance, mice with intestine- and liver-specific FXR ablation (FXRIntestine-/- and FXRLiver-/-, respectively) on an HFD or an HFD containing XN were cognitively tested. XN improved cognitive performance in a genotype- and sex-dependent manner, with improved task learning in females (specifically wild-type), reversal learning in males (specifically wild-type and FXRIntestine-/- mutant) and spatial learning (both sexes). XN increased hippocampal diacylglycerol and sphingomyelin levels in females but decreased them in males. XN increased the ratio of shorter-chain to longer-chain ceramides and hexaceramides. Higher diacylglycerol and lower longer-chain ceramide and hexaceramide levels were linked to improved cognitive performance. Thus, the beneficial sex-dependent cognitive effects of XN are linked to changes in hippocampal diacylglycerol and ceramide levels. This article has an associated First Person interview with the first author of the paper.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.