ArticleCNS neuroscience & therapeutics2025
S-9-PAHSA Protects Against High-Fat Diet-Induced Diabetes-Associated Cognitive Impairment via Gut Microbiota Regulation.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- ZBP1-mediated Treg cell dysfunction exacerbates neuroimmune dysregulation in Alzheimer's disease under metabolic stress.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- CTNNB1 Genetic Variation and Its Interaction With DLK1 in Type 2 Diabetes Mellitus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- 10-Hydroxy-2-decenoic Acid Attenuates Colitis-Associated Cognitive Dysfunction via IFITM3-Related Gut-Brain Axis Inflammation.Journal of agricultural and food chemistry · 2026Article
- The potential connection between inflammatory bowel disease and Alzheimer's disease: mechanistic insights and therapeutic implications.Frontiers in immunology · 2026Review
- Colon-Targeted astragalus polysaccharide nanoparticles prevent NAFLD-Driven hepatocarcinogenesis via microbiota remodeling and NF-κB Inhibition.Journal of experimental & clinical cancer research : CR · 2025Article
- Therapeutic efficacy of rehmannioside A on 5×FAD mice in Alzheimer's disease.Scientific reports · 2025Article
- Exploring associations between nutritional intake and cognitive performance in Spanish older adults.Frontiers in nutrition · 2025Article
- Mechanisms underlying cognitive impairment and management strategies in type 2 diabetes.Frontiers in endocrinology · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
aimDiabetes-associated cognitive impairment (DACI) is a common complication of Type 2 diabetes mellitus (T2DM), with its mechanisms and treatments for DACI remaining incompletely clarified. This study investigated the protective efficacy of the novel lipid S-enantiomer of 9-palmitic acid esters of hydroxy stearic acids (S-9-PAHSA, S9P) in a high-fat diet-induced DACI mouse model.
methodsMice were randomly assigned to three groups: normal diet (ND), high-fat diet (HFD), and HFD + 30 mg/kg/day S9P (HFD + S9P). Fasting blood glucose (FBG), intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were conducted to assess blood glucose homeostasis. Morris Water Maze and Y maze tests evaluated cognitive function, and neuronal status was examined through pathological analysis, Golgi staining, and transmission electron microscopy (TEM). Colonic barrier integrity was assessed using periodic acid-Schiff and Alcian blue staining (AB-PAS) and immunohistochemistry (IHC) staining. Intestinal microbiota composition was analyzed by 16S rDNA sequencing, and serum metabolic characteristics were determined by metabolomics sequencing.
resultsS9P improved glucose homeostasis and alleviated cognitive decline in DACI mice. It also mitigated neuronal damage, dendritic degeneration, and synaptic damage, while restoring colonic barrier integrity and ameliorating gut microbiome imbalances, insulin resistance, and lipid imbalance. Additionally, S9P regulated metabolite profiles and the PI3K/AKT/mTOR signaling pathways, and reduced astrocyte activation and neuroinflammatory responses in the hippocampus of HFD-induced DACI mice.
conclusionS9P had a protective effect against HFD-induced diabetic cognitive impairment closely related to the modulation of the gut-brain axis, suggesting that S9P has the potential to become a new therapeutic approach for DACI.
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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 Socratic graph.