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

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.

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

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.

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.

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.