Naoxintong capsules exhibited a protective effect against cerebral ischemia in the brain hub region of MCAO rats via intervention of amino acid metabolism

Background: Amino acids (AAs) metabolism profiles in brain play a pivotal role in cerebral ischemia (CI), which is a complex, spatial and temporal event. NaoXinTong Capsules (NXT) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. Methods: In this study, a novel analytical method for the quantification of twenty-three AAs in cortex and hippocampus was developed by UPLC-QQQ-MS. Based on middle cerebral artery occlusion (MCAO) rat model, the cerebral infarction and the neurological behavior scores are firstly dynamically evaluated at 3, 12, and 24 h after CI. Then the dynamic levels of the AAs in cortex and hippocampus were analyzed respectively after CI. Results: After CI, MCAO rats showed neurological deficits especially at 24 h. Based on PCA scores plot at different time after CI, the time of the AAs metabolism showing an obvious disturbance in the cortex (12 and 24 h after ischemia) is earlier than that in the hippocampus (24 h after ischemia). Based on the fold-changes of MCAO vs. sham group and receiver operating curve (ROC) analysis, a total of nine AAs biomarkers, with continuous and consistent changes at different time points after CI, were finally obtained including eight AAs of Ala, GABA, Pro, Val, Ile, His, Cit and Leu in the cortex, and three AAs of Ile, Asp, and Cit in the hippocampus. After NXT treatment, the efficacy was confirmed by reducing cerebral infarction and improving the neurological behavior scores. Furthermore, GABA, Pro, His, Leu, Asp, Ile and Cit were found to exhibited an obvious tendency for returning to baseline values in the corresponding regions at 24 h after CI (P