Cynarin inhibits microglia-induced pyroptosis and neuroinflammation via Nrf2/ROS/NLRP3 axis after spinal cord injury.

IF 4.8 3区 医学 Q2 CELL BIOLOGY Inflammation Research Pub Date : 2024-11-01 Epub Date: 2024-09-28 DOI:10.1007/s00011-024-01945-x
Bin Zhang, Jiasheng Yu, Lei Bao, Dongqian Feng, Yong Qin, Daobo Fan, Xin Hong, Yongyi Chen
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Abstract

Background: Spinal cord injury (SCI) elicits excess neuroinflammation and resident microglial pyroptosis, leading further terrible neurological collapse and locomotor dysfunction. However, the current clinical therapy is useless and a feasible treatment is urgent to be explored. Cynarin is a natural component in artichoke playing anti-inflammatory and anti-aging roles in hepatoprotection and cardioprotection, but it is unclear that the pharmacologic action and underlying mechanism of Cynarin in neuropathy.

Methods: Using the SCI mouse model and the BV2 cell line, we here investigated whether Cynarin reduces neuroinflammation and pyroptosis to promote neurological recovery after SCI.

Results: Our results showed that treatment with Cynarin reduces the level of neuroinflammation and microglial pyroptosis. Moreover, the mice treated with Cynarin exhibited lower level of reactive oxygen species (ROS) and cell death, less damage of neurohistology and better locomotor improvement of hindlimbs than the untreated mice and the nuclear factor erythroid 2-related factor 2 (Nrf2)-inhibited mice. Mechanically, Cynarin inhibited the assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by Nrf2-dependent expression to attenuate microglial pyroptosis and neuroinflammation.

Conclusions: To sum up, the current study suggested that administration of Cynarin is a promising compound for anti-neuroinflammation and anti-pyroptosis after SCI. It may be an efficient Nrf2 activator and a NLRP3 inhibitor for microglia in neuropathies.

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脊髓损伤后,仙鹤草苷可通过Nrf2/ROS/NLRP3轴抑制小胶质细胞诱导的脓毒症和神经炎症。
背景:脊髓损伤(SCI)会引起过度的神经炎症和常驻小胶质细胞热解,进一步导致可怕的神经功能衰竭和运动功能障碍。然而,目前的临床疗法毫无用处,迫切需要探索一种可行的治疗方法。洋蓟素是洋蓟中的一种天然成分,具有抗炎、抗衰老、保肝、保心等作用,但洋蓟素在神经病变中的药理作用和内在机制尚不清楚:方法:我们利用 SCI 小鼠模型和 BV2 细胞系,研究 Cynarin 是否能减轻神经炎症和脓毒症,从而促进 SCI 后的神经功能恢复:结果:我们的研究结果表明,Cynarin 可降低神经炎症和小胶质细胞脓毒症水平。此外,与未经治疗的小鼠和核因子红细胞 2 相关因子 2(Nrf2)抑制小鼠相比,Cynarin 治疗小鼠的活性氧(ROS)和细胞死亡水平较低,神经组织学损伤较小,后肢运动能力改善较好。Cynarin通过Nrf2依赖性表达抑制了NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体的组装,从而减轻了小胶质细胞的脓毒症和神经炎症:综上所述,目前的研究表明,Cynarin 是一种具有抗神经炎症和抗脊髓损伤后嗜脓细胞增多作用的化合物。它可能是一种有效的 Nrf2 激活剂和神经病变中小胶质细胞的 NLRP3 抑制剂。
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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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