Mechanism of Velvet Antler Peptide in Preventing Mild Cognitive Impairment Based on Non-Targeted Metabolomics

Velvet antler peptide (VAP) is one of the main active ingredients in Velvet antler (VA), and its mechanism in preventing mild cognitive impairment (MCI) needs to be further studied. In this research, rats model with MCI was established, non-targeted metabonomics method was performed. Total 50 wistar rats were divided into: control, model, piracetam (PIR) , high- and low-dose VAP groups, and were administered for 18 days. Scopolamine (2 mg/kg) was injected intraperitoneally to establish the MCI rat model. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in rat serum were detected by the enzyme-linked immunosorbent assay (ELISA). The expression of B-cell lymphoma/leukemia-(Bcl-2), Bcl-2-associated death promoter (Bad) and Bcl-2-associated IP: 203.8.109.20 On: Thu, 20 Oct 2022 11:01:23 X protein (Bax) in hippocampus of rats wre detetd by Western blot analysis. The brain and kidney of MCI rats were detected by ultra-prformancliquid chromatography/quadrupole timeof-flight mass spectrometry (UPLC-Q/TOF-MS) metabolomics technology, and the differences of metabolites and the dynamic changes of metabolic pathway were analyzed based on the results of Principal Component Analysis (PCA) and Orthogonal partial least squares discriminant analysis (OPLS-DA) The correlation analysis of significantly different metabolites was then analyzed by Cluster analysis (CA), and then the differential metabolite pathway enrichment analysis was performed. According to the statistical analysis of univariate and multivariates, the models constructed between the groups are stable and reliable, the variability and separation trend are good, and there are differences in the metabolomes. In results, VAP increased the content of serum SOD, reduced the content of MDA, increased the expression level of Bcl-2 and reduced the expression level of Bad and Bax protein in MCI model rats. The relevant potential markers in the brain and kidney of MCI rats mainly included folic acid, acetyl L-carnitine (ALC), Prostaglandin E1 (PGE1), 3',5'-cyclicadenosine-monophosphate (cAMP) and various amino acids. Therefore, VAP could inhibit oxidative stress response, reduce hippocampal neuron apoptosis and protect neurons in MCI rats. Its mechanism may be related to regulating folate and lipid metabolism, cyclic adenosine phosphate energy cycle, amino acid biosynthesis and renal secretion of sex hormones.