OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

In order to investigate the effects of pyrolysis conditions on bio-oil production from biomass in molten salt, experiments of biomass pyrolysis were carried out in a self-designed reactor in which the molten salt ZnCl2-KCl (with mole ratio 7/6) was selected as heat carrier, catalyst and dispersion agent. The effects of metal salt added into ZnCl2-KCl and biomass material on biomass pyrolysis were discussed, and the main compositions of bio-oil were determined by GC-MS. Metal salt added into molten salt could affect pyrolysis production yields remarkably. Lanthanon salt could enhance bio-oil yield and decrease water content in bio-oil, when mole fraction of 5.0% LaCl3 was added, bio-oil yield could reach up to 32.0%, and water content of bio-oil could reduce to 61.5%. The bio-oil and char yields were higher when rice straw was pyrolysed, while gas yield was higher when rice husk was used. Metal salts showed great selectivity on compositions of bio-oil. LiCl and FeCl2 promoted biomass to pyrolyse into smaller molecular weight compounds. CrCl3, CaCl2 and LaCl3 could restrain second pyrolysis of bio-oil. The research provided a scientific reference for production of bio-oil from biomass pyrolysis in molten salt.
Biofuels ; analysis ; Bioreactors ; microbiology ; Catalysis ; Chlorides ; chemistry ; Lanthanum ; chemistry ; Lipids ; biosynthesis ; Oryza ; metabolism ; Plant Stems ; metabolism ; Potassium Chloride ; chemistry ; Salts ; chemistry ; Zinc Compounds ; chemistry