黄芪百合颗粒通过HIF-1a/p53/Caspase-3通路减轻低压缺氧所致脑损伤。

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-09-29 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S525602

Xinjue Zhang, Wangjie Cao, Mingyue Pan, Jiawei Huo, Nengxian Zhang, Jiawang Guo, Yong Huang, Yongqi Liu, Hongxia Gong, Yun Su

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引用次数: 0

摘要

背景：高原脑水肿（High altitude cerebral edema， HACE）是一种由急性高原缺氧引起的严重中枢神经系统功能障碍，涉及氧化应激和细胞凋亡。黄芪百合颗粒（HQBHG）对这些过程有一定的抑制作用，但其作用机制尚不清楚。目的：评价黄芪百合颗粒治疗高原脑水肿（HACE）的疗效，并探讨其作用机制。方法：采用UPLC-MS/MS对黄芪百合颗粒的化学成分进行表征。将72只SD大鼠分为6组：无处理对照组（NC）、低压缺氧模型组（HHM）、阳性药物地塞米松（Dex, 5 mg/kg）和HQBHG低、中、高剂量组（1.105 g/kg d、2.21 g/kg d、4.42 g/kg d）。除NC外，所有患者均行72小时6000 m低压缺氧以确定高原脑水肿（HACE）。评估脑屏障通透性（干湿比、Evans Blue染色）、氧化应激标志物（活性氧、超氧化物歧化酶）和组织病理学（HE/Nissl染色）。网络药理学（TCMSP, GenGards， OMIM, Drugbank）和转录组学鉴定了黄芪百合颗粒（HQBHG）的靶点和通路。凋亡信号（HIF-1α/p53/Caspase-3）通过免疫荧光、TUNEL、透射电镜、Western Blotting和qRT-PCR验证。结果：低氧缺氧可引起脑损伤和血脑屏障破坏。黄芪百合颗粒（HQBHG）与HIF-1α/p53/Caspase-3通路相关的网络和转录组分析。黄芪白河颗粒（HQBHG）干预可减轻脑损伤、氧化应激和细胞凋亡，抑制HIF-1α/p53/Caspase-3通路的激活。结论：首次证实黄芪百合颗粒可能通过调节HIF-1α/p53/Caspase-3信号通路、改善低压缺氧引起的血脑屏障破坏、脑组织氧化应激失衡、抑制脑细胞凋亡等机制减轻脑组织损伤。

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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.

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.