Huangqi Baihe Granules Attenuate Hypobaric Hypoxia-Induced Brain Injury via HIF-1a/p53/Caspase-3 Pathway.

BACKGROUND

High altitude cerebral edema (HACE), a severe central nervous system dysfunction caused by acute plateau hypoxia, involves oxidative stress and apoptosis. Huangqi Baihe granules (HQBHG) show efficacy against these processes, but their mechanism remains unclear.

PURPOSE: This study evaluated Huangqi Baihe granules (HQBHG)'s efficacy in treating High altitude cerebral edema (HACE) and elucidated its mechanism.

METHODS

UPLC-MS/MS characterized Huangqi Baihe granules (HQBHG)'s chemical composition. Seventy-two SD rats were divided into six groups: No-treatment Control (NC), Hypobaric Hypoxia Model (HHM), positive drug Dexamethasone (Dex, 5 mg/kg), and HQBHG low/medium/high-dose groups (1.105 g/kg d, 2.21 g/kg d, 4.42 g/kg d). Except NC, all underwent 72-hour 6000 m hypobaric hypoxia to establish High altitude cerebral edema (HACE). Brain barrier permeability (wet-dry ratio, Evans Blue staining), oxidative stress markers (Reactive oxygen species, Superoxide dismutase), and histopathology (HE/Nissl staining) were assessed. Network pharmacology (TCMSP, GenGards, OMIM, Drugbank) and transcriptomics identified Huangqi Baihe granules (HQBHG) targets and pathways. Apoptosis signaling (HIF-1α/p53/Caspase-3) was validated via immunofluorescence, TUNEL, Transmission Electron Microscope, Western Blotting, and qRT-PCR.

RESULTS

Hypobaric hypoxia caused brain injury and blood-brain barrier disruption. Network and transcriptome analyses linked Huangqi Baihe granules (HQBHG)'s effects to HIF-1α/p53/Caspase-3 pathway, involving key genes. Huangqi Baihe granules (HQBHG) intervention attenuated brain injury, oxidative stress, and apoptosis, suppressing HIF-1α/p53/Caspase-3 pathway activation.

CONCLUSION

We demonstrated for the first time that Huangqi Baihe granules (HQBHG) may reduce brain tissue injury by regulating the HIF-1α/p53/Caspase-3 signaling pathway, ameliorating blood-brain barrier disruption induced by low-pressure hypoxia, imbalance of oxidative stress in the brain tissues, and inhibiting apoptosis in the brain cells.