Naofucong improves cognitive function in diabetic rats via the "energy metabolism-histone lactylation modification"...

Diabetic cognitive impairment (DCI) is closely associated with brain energy metabolism disorders. Lactate, acting as both a metabolic intermediate and an epigenetic regulatory molecule in this context, has a crucial impact on neural function through its dynamic balance. This study aimed to explore whether Naofucong (NFC) improves DCI in diabetic rats by regulating hippocampal energy metabolism and histone lactylation modification. Sixty male Sprague - Dawley (SD) rats were used to establish diabetic rat models, which were then divided into control group, diabetic model group, NFC group, and oxamate group, with interventions lasting for 12 weeks. Behavioral tests were conducted to evaluate cognitive function, spatial metabolomics was employed to detect the metabolic function in the hippocampal region, and molecular biological techniques such as CUT&Tag sequencing and Western blotting were used for mechanism exploration. The results showed that NFC significantly improved the cognitive function of diabetic rats. This might be achieved by improving energy metabolism, increasing glutathione content, and regulating the expression of histamine receptor H4 (Hrh4) through altering the lactylation level of histones. This study reveals a novel mechanism by which NFC improves DCI, providing a potential intervention target and theoretical basis for the treatment of DCI.