文献类型：期刊文献

英文题名：A warming-yang herbal decoction protects against high-altitude hypoxia-induced osteoblast injury through modulation of HIF-1 signaling

作者：Liu, Xuehai[1];Qi, Yaqian[1];Zhao, Rui[1];Jia, Binkui[1];Lei, Xilin[1];Li, Hongfan[1];Wang, Di[2];Zhang, Haoling[2];Wang, Wei[3];Song, Zhijing[1,4]

第一作者：刘晓惠

通信作者：Song, ZJ[1];Zhang, HL[2];Wang, W[3];Song, ZJ[4]

机构：[1]Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, Lanzhou, Peoples R China;[2]Univ Sains Malaysia, Adv Med & Dent Inst, Dept Biomed Sci, Minden Heights, Penang, Malaysia;[3]Gansu Univ Chinese Med, Coll Acupuncture Moxibust & Tuina, Lanzhou, Gansu, Peoples R China;[4]Minist Educ, Dunhuang Key Lab Med & Transformat, Lanzhou, Peoples R China

第一机构：甘肃中医药大学中医临床学院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, Lanzhou, Peoples R China;[2]corresponding author), Univ Sains Malaysia, Adv Med & Dent Inst, Dept Biomed Sci, Minden Heights, Penang, Malaysia;[3]corresponding author), Gansu Univ Chinese Med, Coll Acupuncture Moxibust & Tuina, Lanzhou, Gansu, Peoples R China;[4]corresponding author), Minist Educ, Dunhuang Key Lab Med & Transformat, Lanzhou, Peoples R China.|[10735db5df93766a96e5b]甘肃中医药大学针灸推拿学院;[10735]甘肃中医药大学;[10735ccd4a8840d96ab71]甘肃中医药大学中医临床学院;

年份：2025

卷号：16

外文期刊名：FRONTIERS IN PHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-105026379438);WOS:【SCI-EXPANDED(收录号:WOS:001651801600001)】；

基金：The authors declare that financial support was received for the research and/or publication of this article. This work was supported by the Gansu Provincial Department of Science and Technology Joint Fund General Program (No. 24JRRA878), the Gansu Provincial Key Talent Project (No. 2025RCXM006), the "Qihuang Yingcai" Mentor Special Fund of the First-Level Discipline of Traditional Chinese Medicine (No. ZYXKBD-202415), the Gansu Provincial Department of Science and Technology Key R&D Program-International Cooperation (No. 25YFWA024), and the Open Projects of the Ministry of Education Key Laboratory of Dunhuang Medicine and Translational Research (DHYX21-07, DHYX22-05, DHYX23-05), 25JRRA249 Natural Science Foundation of Science and Technology Department of Gansu Province.

语种：英文

外文关键词：high-altitude environment; osteoporosis; HIF-1 signaling pathway; warming yang medicine

摘要：Objective This paper systematically explored dental osteoblast injury at high altitude hypoxic condition and examined the protective role of warming-yang traditional medicine, Aconitum carm michaelii and Zingiber officinale decoction (GAWD) in this condition.Methods We constructed an in-situ high-altitude hypoxic model (4,500 m) with MC3T3-E1 osteoblastic cells and conducted RNA-seq analysis for Differentially Expressed Genes (DEGs). We performed enrichment analyses (GO, KEGG, and the Reactome pathway mapping) to reveal the relationships among the DEGs and key pathways. To further verify our results, we conducted a series of functional assays, including Cell Counting Kit-8 (CCK-8) for cell viability; flow cytometry assessment of reactive oxygen species (ROS); jc-10-based evaluation of mitochondrial membrane potential (MMP), and alkaline phosphatase (ALP) activity serum.Results Transcriptome profiling revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was central in the mediator role of osteoblast injury. High altitude hypoxia greatly suppressed the expression of HIF-1 alpha, HIF-1 beta, von Hippel-Lindau tumor suppressor gene (VHL) and vascular endothelial growth factor (VEGF), resulting in increased intracellular ROS, calcium overload, mitochondrial distress, G1-phase cell cycle arrest, apoptosis, and decreased proliferation. Rehabilitation by GAWD recovered these impairment effects: cell viability and apoptotic protein expression were improved, ROS and intracellular Ca2+ were reduced, and mitochondrial membrane potential was regained, HIF-1/VEGF axis was recovered, apoptotic signaling and gross morphological injury were attenuated, and overall osteoblastic function was restored.Conclusion The findings implicated HIF-1 signaling dysregulation in inducing high-altitude hypoxia-induced osteoblast injury and osteoporosis. GAWD may reduce hypoxia-induced cellular stress through recovering redox homeostasis and adjusting HIF-1/VEGF signaling. Collectively, this, study offers early molecular evidence supporting the utility of GAWD as a traditional Chinese medicine-based intervention for the prevention of bone metabolic disorders due to chronic hypoxic exposure.