Serum lipidomics reveal the mechanism of memory disorder improvement by Qifu decoction

Abstract

Memory disorder (MD) is a neurodegenerative disease that seriously affects the quality of life of the elderly in China. It is characterized by cognitive deficits and psychiatric symptoms. In addition to oxidative damage, neurotransmitter disorders, and other factors, Ca²⁺ homeostasis and lipid metabolism are among the major pathways of MD etiology. Studies have shown that Ca²⁺ influx, causing Ca²⁺ overload, leads to neuronal apoptosis and alterations in lipid metabolites at all MD stages. Qifu decoction (QFD) is one of the classic compounds for the traditional treatment of dementia, which has been shown to significantly improve MD caused by dementia and Alzheimer's disease (AD). So far, it is not clear whether QFD can regulate Ca²⁺ homeostasis and lipids to improve MD. In this study, we developed a scopolamine hydrobromide MD mouse model and performed neurobehavioral experiments and examinations of brain tissue pathology, Ca²⁺ homeostasis-related factor levels, and non-targeted lipidomics to explore the mechanism of QFD action in improving MD. The results showed that four weeks of intragastric administration of QFD resulted in significant increases in the cognitive ability and spatial memory ability of the mice with MD. Furthermore, the damage to nerve cells was reduced, the levels of Ca²⁺ and CaM in the serum were decreased, whereas the content of CaMKII was increased, and the Ca²⁺ homeostasis was regulated. Non-targeted lipidomics detected four lipid subclasses and 17 potential differential metabolites. Metabolic pathway analysis revealed that QFD significantly regulated sphingolipid metabolism and improved MD. In summary, QFD improves scopolamine hydrobromide memory impairment in mice by regulating the Ca²⁺ signaling pathway and sphingolipid metabolism. This study provides new insights into the beneficial mechanism of QFD on MD from the perspective of lipidomics.