Mechanism of Action of Velvet Antler Polypeptide in Improving Mild Cognitive Impairment in Rats

ABSTRACT This study aimed to elucidate the mechanism of velvet antler polypeptide (VAP) in improvement of learning and memory function in mild cognitive impairment (MCI) rats model, specifically by investigating the PI3K, AKT and mTOR pathway. The type and content of amino acids (AA) in VAP were determined using pre-column derivatization-high performance liquid chromatography (PD-HPLC). Wistar rats were randomly divided into 5 groups (n=10 per group): control, model, piracetam (PIR), VAPH (300 mg/ kg VAP) and VAPL (200 mg/kg VAP) groups. After intragastric administration, the rats' behavioral indexes were observed through the open field test (OFT), and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in serum were detected using ELISA. The protein expression levels of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in the hippocampus were detected through western blotting. In the results, VAP contained 17 kinds of AA, including 7 essential AA, with a content of 394.08 g/kg, the total AA content was 831.55 g/kg. In the OFT, the PIR, VAPH and VAPL groups showed significant decreases in slient period, significant increases in exercise time and behavior path, and center residence time in the PIR and VAPH groups were also increased significantly. The MDA content in serum of PIR, VAPH and VAPL groups significantly decreased, while the SOD, BDNF and NGF content in serum of PIR and VAPH groups significantly increased. The expression levels of PI3K and mTOR in the hippocampus of PIR, VAPH and VAPL groups were significantly increased, and the expression level of Akt in the hippocampus of PIR and VAPH groups was significantly increased. In summary, VAP could improve the learning and memory abilities of MCI model rats, and its mechanism may be related to the regulation of PI3K, Akt and mTOR expression levels in the hippocampus of rats. This study provides a basis for further development and utilization of VAP and a better understanding of its mechanism of improving MCI.