Gastrodin Enhances Hypoxia Tolerance in Mice via the PI3K/AKT/HIF-1α Signaling Pathway
BAI Shuai
LIU Wei
XU Yi
LIU Shulei
Abstract：Objective To investigate the effect of gastrodin on hypoxia tolerance in the central nervous system of mice and its molecular mechanism.Methods Forty healthy BALB/c mice were randomly divided into four groups(n=10 per group):control group,hypoxia preconditioning group,low-dose gastrodin group(20 mg/kg),and high-dose gastrodin group(100 mg/kg).The experimental groups received intraperitoneal injections twice daily for 7 consecutive days.Hypoxia tolerance time and oxygen consumption were compared among the groups.The mRNA and protein expression levels of phosphoinositide 3-kinase(PI3K),protein kinase B(AKT),and hypoxia-inducible factor-1α(HIF-1α)in brain tissues were detected using RT-qPCR and Western blotting.In vitro experiments using primary cultured rat cortical neurons included the following groups:gastrodin control,acute hypoxia,hypoxia preconditioning,and different concentrations of gastrodin treatment(0.1 mmol/L and 0.4 mmol/L).Neuronal viability was assessed using the CCK-8 assay.Results Compared with the control group,both the hypoxia preconditioning group and the high-dose gastrodin group showed significantly prolonged hypoxia tolerance time(P<0.05),but only the high-dose gastrodin group exhibited a significant decrease in oxygen consumption(P<0.05).Molecular analysis revealed that the high-dose gastrodin group had significantly upregulated mRNA and protein expression of PI3K,AKT,and HIF-1α(P<0.05),while only HIF-1α expression was significantly increased in the low-dose gastrodin group(P<0.05).In vitro experiments confirmed that 0.4 mmol/L gastrodin significantly improved neuronal viability under hypoxic conditions(P<0.05).Conclusion Gastrodin can effectively enhance hypoxia tolerance in the central nervous system,and its mechanism is closely associated with activation of the PI3K/AKT/HIF-1α signaling pathway.Hypoxia preconditioning shares the same molecular regulatory mechanism.
Keywords：gastrodinhypoxia tolerancePI3K/AKT signaling pathwayhypoxia-inducible factor-1α
Publication Date：2026-01-20
Online Publishing Date：2026-01-24(First online date of this platform, not the publication date of the document)
Pages：6( 148-153 )