Spinal cord injury (SCI) is a severe neurological disease; however, there is no effective treatment for spinal cord injury. Neuroinflammation involves the activation of resident microglia and the infiltration of macrophages is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Parthenolide (PN) has been reported to exert anti-inflammatory effects in fever, migraines, arthritis, and superficial inflammation; however, the role of PN in SCI therapeutics has not been clarified. In this study, we showed that PN could improve the functional recovery of spinal cord in mice as revealed by increased BMS scores and decreased cavity of spinal cord injury in vivo. Immunofluorescence staining experiments confirmed that PN could promote axonal regeneration, increase myelin reconstitution, reduce chondroitin sulfate formation, inhibit scar hyperplasia, suppress the activation of A1 neurotoxic reactive astrocytes and facilitate shift from M1 to M2 polarization of microglia/macrophages. To verify how PN exerts its effects on microglia/macrophages polarization, we performed the mechanism study in vitro in microglia cell line BV-2. PN could significantly reduce M1 polarization in BV2 cells and partially rescue the decrease in the expression of M2 phenotype markers of microglia/macrophage induced by LPS, but no significant effect on M2 polarization stimulated with IL-4 was observed. Further study demonstrated PN inhibited NF-κB signal pathway directly or indirectly, and suppressed activation of signal transducer and activator of transcription 1 or 3 (STAT1/3) via reducing the expression of HDAC1 and subsequently increasing the levels of STAT1/3 acetylation. Overall, our study illustrated that PN may be a promising strategy for traumatic SCI.

脊髓损伤（SCI）是一种严重的神经系统疾病；然而，脊髓损伤没有有效的治疗方法。神经炎症涉及常驻小胶质细胞的激活和巨噬细胞的浸润是SCI继发性损伤的主要发病机制，被认为是SCI的治疗靶点。据报道，小白菊内酯 (PN) 对发烧、偏头痛、关节炎和浅表炎症具有抗炎作用；然而，PN 在 SCI 治疗中的作用尚未明确。在这项研究中，我们通过增加 BMS 评分和减少体内脊髓损伤空腔来证明 PN 可以改善小鼠脊髓的功能恢复。免疫荧光染色实验证实，PN可以促进轴突再生，增加髓磷脂重建，减少硫酸软骨素形成，抑制疤痕增生，抑制A1神经毒性反应性星形胶质细胞的活化，并促进小胶质细胞/巨噬细胞从M1极化转向M2极化。为了验证PN如何对小胶质细胞/巨噬细胞极化发挥作用，我们在小胶质细胞系BV-2中进行了体外机制研究。PN可显着降低BV2细胞的M1极化，并部分挽救LPS诱导的小胶质细胞/巨噬细胞M2表型标志物表达的降低，但对IL-4刺激的M2极化没有明显影响。进一步研究表明PN直接或间接抑制NF-κB信号通路，并通过降低HDAC1的表达并随后增加STAT1/3乙酰化水平来抑制信号转导子和转录激活子1或3（STAT1/3）的激活。总体而言，我们的研究表明 PN 可能是治疗创伤性 SCI 的一种有前途的策略。