Naringenin alleviates bone cancer pain in rats via down-regulating spinal P2X7R /PI3K/AKT signaling: involving suppression in spinal inflammation,Molecular & Cellular Toxicology

当前位置： X-MOL 学术 › Mol. Cell. Toxicol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Naringenin alleviates bone cancer pain in rats via down-regulating spinal P2X7R /PI3K/AKT signaling: involving suppression in spinal inflammation
Molecular & Cellular Toxicology ( IF 1.1 ) Pub Date : 2021-07-19 , DOI: 10.1007/s13273-021-00156-3
Jian-Gang Song ₁ , Lv Liu ₂

Affiliation

Background

Bone cancer pain (BCP) seriously affects patient’s quality of life, which remains a difficult clinical problem, lacking effective drugs for treating it. The inflammation in the spinal cord involves the pathogenesis of BCP. The inhibition of spinal phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway or spinal P2X7 receptor (P2X7R) has previously been shown to alleviate BCP. Naringenin (NAR) has analgesic role and anti-inflammatory property.

Objective

The present study investigated the protection of NAR against BCP and explored whether the inhibition of spinal inflammation and the blockade of spinal P2X7R/PI3K/AKT signaling involved in this protection.

Result

NAR significantly alleviated mechanical allodynia (the increase of paw withdrawal threshold in Von Frey test) and thermal hyperalgesia (the increase of paw withdrawal latency in Hargreaves test) in BCP rats. Additionally, NAR inhibited inflammatory cytokines (the reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were measured using Elisa assay) and down-regulated P2X7R/PI3K/AKT signaling (the decreased P2X7R expression, the reduced ratios of phosphorylated (p)-PI3K/PI3K and p-AKT/AKT, which were detected Western blot) in the spinal cord of BCP rats.

Conclusion

NAR alleviated BCP through inhibiting inflammatory cytokines and down-regulating P2X7R/PI3K/AKT signaling in the spinal cord of rats. These findings revealed that NAR, as an effective agent against BCP, may provide an effective approach in the management of bone cancer patients.

Graphic abstract

中文翻译：

柚皮素通过下调脊髓 P2X7R/PI3K/AKT 信号传导减轻大鼠骨癌疼痛：涉及抑制脊髓炎症

背景

骨癌痛（BCP）严重影响患者的生活质量，目前仍是临床难题，缺乏有效的药物治疗。脊髓中的炎症涉及 BCP 的发病机制。先前已证明抑制脊髓磷脂酰肌醇 3-激酶 (PI3K)/蛋白激酶 B (AKT) 信号通路或脊髓 P2X7 受体 (P2X7R) 可减轻 BCP。柚皮素 (NAR) 具有镇痛作用和抗炎特性。

客观的

本研究调查了 NAR 对 BCP 的保护作用，并探讨了脊髓炎症的抑制和脊髓 P2X7R/PI3K/AKT 信号传导的阻断是否参与了这种保护。

结果

NAR 显着减轻 BCP 大鼠的机械异常性疼痛（Von Frey 试验中缩爪阈值的增加）和热痛觉过敏（Hargreaves 试验中缩爪潜伏期的增加）。此外，NAR 抑制炎性细胞因子（使用 Elisa 测定法测量降低的肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）和白介素-6（IL-6）水平）并下调 P2X7R BCP 大鼠脊髓中的 /PI3K/AKT 信号传导（P2X7R 表达降低，磷酸化 (p)-PI3K/PI3K 和 p-AKT/AKT 的比率降低，蛋白质印迹检测到这些）。