Bacopa monnieri Extract Diminish Hypoxia-Induced Anxiety by Regulating HIF-1α Signaling and Enhancing the Antioxidant Defense System in Hippocampus.

Abstract

Hypoxia is a significant stressor, and stabilized hypoxia-inducible factor-1α (HIF-1α) regulates the expression of numerous genes, leading to various biochemical, molecular, physiological and genomic changes. The body's oxygen-sensing system activates gene expression to protect brain tissues from hypoxia. Gamma-aminobutyric acid, an inhibitory neurotransmitter, regulates brain excitability during hypoxia through the activation of HIF-1 α. Herbal medicines have been widely used for managing various toxicological effects and disorders including hypoxia; however, the data on safety, efficacy and the molecular mechanisms that increase vulnerability or lethality against hypoxia are still lacking and urgently need to be investigated. The Current study aims to investigate how Bacopa monnieri extract (BME), specially CDRI-08 affects the hippocampus of mice subjected to conditions that simulate hypoxia. The pre and co-treatment of mice involved administrating BME (200 mg/kg BW) for 14 days, followed by exposure to CoCl₂ (40 mg/kg BW). BME decreased the levels of reactive oxygen species (ROS) and lipid peroxidation, while it increased the Gamma-aminobutyric acid receptor subunit-ɑ1 (GABAAR-ɑ1) level as well as the activity of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Furthermore BME reduced the levels of HIF-1α and its downstream targets glucose transporter-1 (GLUT-1) and erythropoietin (EPO) in the DG, CA1, and CA3 regions of hippocampus. Additionally, results obtained from the open field, elevated zero maze and plus maze tests indicate that BME restores anxiety caused by hypoxia. Together, these findings suggested that BME mitigates the harmful effects of oxidative stress and altered hypoxia related signaling in hippocampus; and may provide a basis for its therapeutic use in the recovery from hypoxia-led anxiety.