Investigating the mechanism of Qifu Yin in ameliorating memory disorders through pseudo-targeted lipidomics†

Memory disorder (MD) is a neurodegenerative disease with an increasing incidence rate that adversely affects the quality of life of patients. Qifu Yin (QFY), a classic traditional Chinese medicine formula used for treating dementia, is known for its neuroprotective properties, although its mechanism of action requires further exploration. In this study, D-galactose combined with aluminum chloride was used to establish an MD rat model, and behavior, histopathology, and related indicators were used to evaluate the pharmacodynamics of the formula in the rats. Furthermore, brain tissues were examined using pseudo-targeted lipidomics analysis, and candidate ion pairs were screened through mass spectrometry using UPLC-Q/Orbitrap HRMS. An sMRM detection method for candidate ion pairs was developed using UHPLC-Q-TRAP-MS/MS and validated. This approach was applied to the lipidomics study of QFY in improving MD. Differential metabolites screened through pseudo-targeted lipidomics were analyzed by employing network pharmacology, and the pathway was verified to explore their mechanism of action. Results demonstrated that QFY could improve memory impairment. A total of 1052 ion pairs were constructed in the pseudo-targeted lipidomics analysis, identifying 33 differential metabolites and 5 metabolic pathways. Furthermore, 31 differential metabolites in MD rats treated with QFY were significantly reversed. Immunohistochemical analysis showed that QFY could inhibit the expression of inflammatory factors. Network pharmacological analysis showed that the calcium signaling pathway was the main signaling pathway, and QFY could significantly reverse the expression levels of mRNA and protein. Thus, QFY can improve memory impairment in rats, which may be related to the regulation of oxidative stress, lipid metabolism disorder and the calcium signaling pathway.