108605
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
基于转录组学分析和实验验证，6-羟基黄酮通过激活 PI3K/AKT 信号通路改善高原脑损伤
Authors Xin Y, Wang G, Yang C, Ma H, Jing L
Received 30 March 2025
Accepted for publication 18 September 2025
Published 23 September 2025 Volume 2025:19 Pages 8641—8656
DOI https://doi.org/10.2147/DDDT.S526988
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Leonidas Panos
Yu Xin,1,2 Gege Wang,2 Chenyu Yang,2 Huiping Ma,2 Linlin Jing1,2
1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Pharmacy, The 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou, Gansu, 730050, People’s Republic of China
Correspondence: Linlin Jing, Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi’an, Shaanxi, 710061, People’s Republic of China, Email jinglinlin@xjtufh.edu.cn Huiping Ma, Department of pharmacy, The 940th Hospital of Joint Logistics Support force of PLA, No. 333 Binhe South Road, Qilihe District, Lanzhou, 730050, Gansu, People’s Republic of China, Email huipingmacyk@163.com
Purpose: Our Prior research has shown that 6-hydroxygenistein (6-OHG) alleviates hypobaric hypoxia induced brain injury (HHBI) achieved by its powerful antioxidant, anti-inflammatory, and anti-apoptotic capabilities, but its mechanism still requires additional investigation. The objective of this study was to uncover the protective mechanism of 6-OHG against HHBI based on transcriptomics analysis and experimental validation.
Methods: The gene levels in brain tissue obtained from previous study were accessed via the RNA-Seq technique. DESeq2 R package was used to identify the differentially expressed genes (DEGs). Functional enrichment analysis and molecular docking were investigated utilizing the clusterProfiler R package and Autodock Vina software, respectively. In experimental validation stage, histological analysis was performed using Hematoxylin-Eosin (HE) staining. Oxidative stress, inflammatory, and apoptotic indexes in brain tissue were measured using commercial kits. Western blot was applied for detecting related protein expression.
Results: The RNA-Seq analysis revealed 905 differentially expressed genes (DEGs) between the Con and Mod groups, with 239 upregulated and 666 downregulated. Between the 6-OHG and Mod groups, there were 192 DEGs, including 98 upregulated and 94 downregulated genes. Go and KEGG function analyses highlighted the PI3K/AKT signaling pathway as a crucial regulatory mechanism. Western blot analysis showed that HH exposure caused a decrease in the ratios of p-PI3K/PI3K and p-AKT/AKT in the mouse brain, but this effect was reversed by 6-OHG treatment, indicating that 6-OHG activates the PI3K/AKT signaling pathway. Furthermore, LY294002, a selective PI3K inhibitor, effectively blocked this activation and also abolished the protective effects of 6-OHG on histopathological damage, as well as its antioxidant, anti-inflammatory, and anti-apoptotic activities in HHBI mice.
Conclusion: 6-OHG mitigates HHBI by activating the PI3K/AKT signaling pathway, suggesting its potential therapeutic application for HHBI treatment.
Keywords: 6-hydroxygenistein, transcriptomics, therapeutic target, hypobaric hypoxia induced brain damage, PI3K/AKT signaling pathway
1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Pharmacy, The 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou, Gansu, 730050, People’s Republic of China
Correspondence: Linlin Jing, Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi’an, Shaanxi, 710061, People’s Republic of China, Email jinglinlin@xjtufh.edu.cn Huiping Ma, Department of pharmacy, The 940th Hospital of Joint Logistics Support force of PLA, No. 333 Binhe South Road, Qilihe District, Lanzhou, 730050, Gansu, People’s Republic of China, Email huipingmacyk@163.com
Purpose: Our Prior research has shown that 6-hydroxygenistein (6-OHG) alleviates hypobaric hypoxia induced brain injury (HHBI) achieved by its powerful antioxidant, anti-inflammatory, and anti-apoptotic capabilities, but its mechanism still requires additional investigation. The objective of this study was to uncover the protective mechanism of 6-OHG against HHBI based on transcriptomics analysis and experimental validation.
Methods: The gene levels in brain tissue obtained from previous study were accessed via the RNA-Seq technique. DESeq2 R package was used to identify the differentially expressed genes (DEGs). Functional enrichment analysis and molecular docking were investigated utilizing the clusterProfiler R package and Autodock Vina software, respectively. In experimental validation stage, histological analysis was performed using Hematoxylin-Eosin (HE) staining. Oxidative stress, inflammatory, and apoptotic indexes in brain tissue were measured using commercial kits. Western blot was applied for detecting related protein expression.
Results: The RNA-Seq analysis revealed 905 differentially expressed genes (DEGs) between the Con and Mod groups, with 239 upregulated and 666 downregulated. Between the 6-OHG and Mod groups, there were 192 DEGs, including 98 upregulated and 94 downregulated genes. Go and KEGG function analyses highlighted the PI3K/AKT signaling pathway as a crucial regulatory mechanism. Western blot analysis showed that HH exposure caused a decrease in the ratios of p-PI3K/PI3K and p-AKT/AKT in the mouse brain, but this effect was reversed by 6-OHG treatment, indicating that 6-OHG activates the PI3K/AKT signaling pathway. Furthermore, LY294002, a selective PI3K inhibitor, effectively blocked this activation and also abolished the protective effects of 6-OHG on histopathological damage, as well as its antioxidant, anti-inflammatory, and anti-apoptotic activities in HHBI mice.
Conclusion: 6-OHG mitigates HHBI by activating the PI3K/AKT signaling pathway, suggesting its potential therapeutic application for HHBI treatment.
Keywords: 6-hydroxygenistein, transcriptomics, therapeutic target, hypobaric hypoxia induced brain damage, PI3K/AKT signaling pathway