Harmine-mediated Reduction of Bone Cancer Pain in Rats Correlates With Suppressed DYRK1A/NF-κB Signaling Axis.

IF 2.5 4区医学 Q3 NEUROSCIENCES

Journal of integrative neuroscience Pub Date : 2025-06-23 DOI:10.31083/JIN38100

Shuyao Zhang, Shang Zheng, Jia Jin, Yuhua Li, Liping Chen, Junjie Lin, Ming Yao, Longsheng Xu

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引用次数: 0

Abstract

Background: Bone cancer pain (BCP) is a prevalent chronic pain condition and a common clinical symptom in patients with advanced cancer. It significantly affects the mobility and quality of life of patients; however, current treatments offer limited efficacy. Harmine, a beta-carboline alkaloid extracted from Peganum harmala, exhibits anti-inflammatory, anxiolytic, analgesic, and neuroprotective properties. However, its antinociceptive properties and mechanisms in BCP models remain unclear. This study aimed to systematically investigate the analgesic effects of Harmine in rats with BCP and explore its underlying molecular mechanisms.

Methods: Using databases such as SwissTargetPrediction and Polypharmacology Browser, molecular docking analysis, behavioral tests, and biochemical analysis, we comprehensively evaluated the effects of Harmine in the BCP model.

Results: The results demonstrated that Harmine significantly alleviated BCP induced by Luciferin-Malignant Atypical Discrete Breast 106 cells (LUC-MADB106) in a dose-dependent manner. Intrathecal administration of Harmine significantly inhibited the upregulation of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) expression and the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in the spinal cord dorsal horn (SCDH) of rats with bone cancer.

Conclusions: These findings suggest that Harmine has significant therapeutic potential for alleviating BCP hyperalgesia, providing a foundation for the future development of new drugs targeting BCP.

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毒胺介导的大鼠骨癌疼痛减轻与抑制DYRK1A/NF-κB信号轴相关。

背景：骨癌疼痛（BCP）是一种常见的慢性疼痛，是晚期癌症患者常见的临床症状。显著影响患者的活动能力和生活质量；然而，目前的治疗方法疗效有限。咸草碱是一种从咸草中提取的-碳碱生物碱，具有抗炎、抗焦虑、镇痛和神经保护作用。然而，在BCP模型中，其抗感知特性和机制尚不清楚。本研究旨在系统研究鼠碱对BCP大鼠的镇痛作用，并探讨其可能的分子机制。方法：利用SwissTargetPrediction、Polypharmacology Browser等数据库，结合分子对接分析、行为测试、生化分析等方法，综合评价鼠碱对BCP模型的影响。结果：鼠碱能显著减轻荧光素-恶性非典型离散乳腺106细胞（LUC-MADB106）诱导的BCP，且呈剂量依赖性。鞘内给药鼠碱可显著抑制骨癌大鼠脊髓背角（SCDH）双特异性酪氨酸磷酸化调节激酶1A （DYRK1A）表达上调和活化B细胞核因子κB轻链增强子（NF-κB）通路的激活。结论：本研究结果提示，苦毒碱在缓解BCP痛觉过敏方面具有显著的治疗潜力，为今后开发针对BCP的新药奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of integrative neuroscience 医学-神经科学

CiteScore

2.80

自引率

5.60%

发文量

173

审稿时长

2 months

期刊介绍： JIN is an international peer-reviewed, open access journal. JIN publishes leading-edge research at the interface of theoretical and experimental neuroscience, focusing across hierarchical levels of brain organization to better understand how diverse functions are integrated. We encourage submissions from scientists of all specialties that relate to brain functioning.