已发表论文

黄芪白合颗粒通过 HIF-1α/p53/Caspase-3 通路减轻低气压缺氧所致脑损伤

 

Authors Zhang X, Cao W, Pan M, Huo J, Zhang N, Guo J, Huang Y, Liu Y , Gong H, Su Y

Received 28 February 2025

Accepted for publication 20 July 2025

Published 29 September 2025 Volume 2025:19 Pages 8823—8841

DOI https://doi.org/10.2147/DDDT.S525602

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Solomon Tadesse Zeleke

Xinjue Zhang,1,2,* Wangjie Cao,1,2,* Mingyue Pan,1,2 Jiawei Huo,1,2 Nengxian Zhang,1,2 Jiawang Guo,1,2 Yong Huang,1,2 Yongqi Liu,1,2 Hongxia Gong,1,2 Yun Su1,2,* 

1Gansu University Key Laboratory for Molecular Medicine & Chinese Medicine Prevention and Treatment of Major Diseases, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, 730000, People’s Republic of China; 2Key Laboratory of Dunhuang Medicine, Ministry of Education, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yun Su, School of Basic Medical Sciences, Gansu University of Traditional Chinese Medicine, Lanzhou, 730050, People’s Republic of China, Email suyungszy@126.com

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.

Keywords: Huangqi Baihe Granule, hypobaric hypoxia, high altitude cerebral edema, HIF-1α/p53/caspase-3, apoptosis