ArticleFrontiers in immunology2026
Protective effect and mechanisms of Buyang Huanwu decoction against hypobaric hypoxia-induced brain injury in mice: involvement of inflammatory responses and HIF-1/PI3K-Akt-related pathways.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background/objectives: This study aimed to investigate the preventive and protective effect of Buyang Huanwu Decoction (BHD) against hypobaric hypoxia-induced brain injury in mice and to explore its underlying mechanisms. Particular emphasis was placed on evaluating whether BHD pretreatment could prevent or attenuate hypobaric hypoxia-induced neurological dysfunction and hippocampal injury, and on clarifying its potential mechanisms from the perspectives of inflammatory responses, metabolic regulation, and HIF-1/PI3K-Akt-related pathways. Methods: A mouse model of hypobaric hypoxia-induced brain injury was established by exposure to a simulated high-altitude hypoxic environment equivalent to an altitude of 6000 m for 72 h. Mice were assigned to the normal control, model, BHD-pretreated, and acetazolamide-positive control groups. BHD and acetazolamide were administered once daily by intragastric gavage, starting 4 days before hypobaric hypoxia exposure and continuing during the 72 h exposure period. Open field testing was performed to assess spontaneous locomotor activity and exploratory behavior. Hippocampal injury was evaluated by hematoxylin and eosin staining, Nissl staining, and HIF-1α immunofluorescence staining. Non-targeted serum metabolomics, network pharmacology, hippocampal transcriptomics, and RT-qPCR validation were integrated to explore the potential mechanisms of BHD pretreatment. Results: BHD pretreatment prevented hypobaric hypoxia-induced behavioral abnormalities and alleviated hippocampal pathological injury, neuronal loss, and Nissl body reduction. BHD also reduced excessive hippocampal HIF-1α expression. Multi-omics analyses suggested that the protective effect of BHD was associated with the regulation of inflammatory responses, metabolic disturbances, and HIF-1/PI3K-Akt-related signaling. RT-qPCR validation showed that BHD modulated the abnormal expression of HIF-1α, IL-6, VEGFA, NF-κB1, and STX1A in hippocampal tissue. Conclusions: BHD exerts a preventive neuroprotective effect against hypobaric hypoxia-induced brain injury in mice. Its effects may involve coordinated regulation of hypoxic responses, inflammatory signaling, metabolic remodeling, and HIF-1/PI3K-Akt-related pathways.
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