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dc.contributor.authorThura Tun Ooen_US
dc.contributor.authorNatticha Sumneangen_US
dc.contributor.authorBenjamin Ongnoken_US
dc.contributor.authorBusarin Arunsaken_US
dc.contributor.authorTitikorn Chunchaien_US
dc.contributor.authorSasiwan Kerdphooen_US
dc.contributor.authorNattayaporn Apaijaien_US
dc.contributor.authorWasana Pratchayasakulen_US
dc.contributor.authorGuang Liangen_US
dc.contributor.authorNipon Chattipakornen_US
dc.contributor.authorSiriporn C. Chattipakornen_US
dc.description.abstractBackground and Purpose: Chronic high-fat diet (HFD) intake instigates prediabetes and brain pathologies, which include cognitive decline and neuroinflammation. The myeloid differentiation factor 2 (MD-2)/toll-like receptor 4 (TLR4) complex plays a pivotal role in neuroinflammation. The MD-2 inhibitor (L6H21) reduces systemic inflammation and metabolic disturbances in HFD-induced prediabetes. However, the potential role of L6H21, and its comparison with metformin, on brain pathologies in HFD-induced prediabetes has never been investigated. Experimental Approach: Male Wistar rats were given either a normal diet (ND) (n = 8) or a HFD (n = 104) for 16 weeks. At the 13th week, ND-fed rats were given a vehicle, whereas HFD-fed rats were randomly divided into 13 subgroups. Each subgroup was given vehicle, L6H21 (three doses) or metformin (300-mg·kg−1·day−1) for 1, 2 or 4 weeks. Metabolic parameters, cognitive function, brain mitochondrial function, brain TLR4–MD-2 signalling, microglial morphology, brain oxidative stress, brain cell death and dendritic spine density were investigated. Key Results: HFD-fed rats developed prediabetes, neuroinflammation, brain pathologies and cognitive impairment. All doses of L6H21 and metformin given to HFD-fed rats at 2 and 4 weeks attenuated metabolic disturbance. Conclusion and Implications: In rats, L6H21 and metformin restored cognition and attenuated brain pathologies dose and time-dependently. These results indicate a neuroprotective role of MD-2 inhibitor in a model of prediabetes.en_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleL6H21 protects against cognitive impairment and brain pathologies via toll-like receptor 4–myeloid differentiation factor 2 signalling in prediabetic ratsen_US
article.title.sourcetitleBritish Journal of Pharmacologyen_US
article.volume179en_US Medical Universityen_US Mai Universityen_US
Appears in Collections:CMUL: Journal Articles

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