Protective Effect of Polysaccharide against Acute High-Altitude Hypoxia-Induced Brain Injury and Its Metabolomics.

L., a traditional Tibetan medicine, has been wildly used for treating plateau disease. Polysaccharide is an important chemical component in . The present study aimed to evaluate the effect of polysaccharide (BRP) against acute high-altitude hypoxia (AHH) induced brain injury and its metabolic mechanism. The rats were randomly divided into six groups: control group, AHH group, Hongjingtian oral liquid group, and three BRP groups (38, 75, and 150 mg/kg/d). Serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were detected by commercial biochemical kits. Hippocampus and cortex histopathological changes were observed by H&E staining and Nissl staining. Neuronal apoptosis was observed by TUNEL staining. The protein and gene expression of Caspase-3, Bax, Bcl-2, p-PI3K, PI3K, p-Akt, Akt, HIF-1, microRNA 210, ISCU1/2, and COX10 were detected by western blotting and qRT-PCR. Then, a brain metabolomics method based on UPLC-Q-Exactive-MS was performed to discover potential biomarkers and analyze metabolic pathways. It was found that BRP decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, reduced the pathological changes, inhibited apoptosis, and activated the PI3K/Akt/HIF-1 signaling pathway as evidenced by increased phosphorylation of PI3K and Akt, enhanced protein expression of HIF-1 and gene levels of microRNA210, ISCU1/2, and COX10. Furthermore, 15 endogenous potential biomarkers were identified in the brain through metabolomics analysis. BRP can regulate 7 potential biomarkers and the corresponding metabolic pathways were mainly associated with pyruvate metabolism and glycolysis/gluconeogenesis. Collectively, BRP has a clear protective effect on AHH-induced brain injury and its mechanisms may be related to ameliorate oxidative stress injury, inhibit apoptosis by activating PI3K/Akt/HIF-1 signaling pathway, and reverse metabolic pathway disturbances.