Background. Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability. CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy. Wild bitter melon (WBM; Momordica charantia Linn. var. abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid (α-ESA), a peroxisome proliferator-activated receptor-β (PPAR-β) ligand. Activated PPAR-β inhibits the nuclear factor κB (NF-κB) signaling pathway via the inhibition of IκB (inhibitor of NF-κB) degradation. The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown. Materials and Methods. A mouse model of SCI was generated via spinal cord hemisection. The SCI mice were administered WBM intraperitoneally (500 mg/kg bodyweight). Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an in vitro model for studying astrocyte-mediated inflammation post-SCI. The roles of CISD2 and PPAR-β in inflammatory signaling were examined using LPS-stimulated SH-SY5Y cells transfected with si-CISD2 or scramble RNA. Results. WBM mitigated the SCI-induced downregulation of CISD2, PPAR-β, and IκB and upregulation of glial fibrillary acidic protein (GFAP; marker of astrocyte reactivation) in the spinal cord of SCI mice. Additionally, WBM (1 μg/mL) mitigated LPS-induced CISD2 downregulation. Furthermore, SH-SY5Y neural cells with CISD2 knockdown exhibited decreased PPAR-β expression and augmented NF-κB signaling. Conclusion. To the best of our knowledge, this is the first study to report that CISD2 is an upstream modulator of the PPAR-β/NF-κB proinflammatory signaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI mice and LPS-stimulated ALT astrocytes.

中文翻译：

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野生苦瓜通过上调脊髓损伤后损伤减弱的 CISD2 表达发挥抗炎作用

背景。脊髓损伤 (SCIs) 通过星形胶质细胞再激活诱导继发性神经炎症，这对神经元存活产生不利影响并最终导致长期残疾。据报道，CDGSH 铁硫域 2 (CISD2) 参与介导抗炎反应，可作为 SCI 治疗的靶点。野生苦瓜 (WBM; Momordica charantia Linn. var. abbreviata Ser.) 含有一种称为 α-桐酸 ( α -ESA)的抗炎剂，它是一种过氧化物酶体增殖物激活受体-β (PPAR- β ) 配体。活化的 PPAR- β抑制核因子κ B (NF- κB) 通过抑制IκB （NF- κB抑制剂）降解的信号通路。星形胶质细胞失活和 CISD2 在急性 SCI 中 WBM 抗炎机制中的作用尚不清楚。材料和方法。通过脊髓半切产生SCI小鼠模型。对 SCI 小鼠进行 WBM 腹膜内给药（500 mg/kg 体重）。脂多糖（LPS-）刺激的 ALT 细胞（星形胶质细胞）被用作体外模型，用于研究 SCI 后星形胶质细胞介导的炎症。使用转染 si-CISD2 或乱序 RNA 的 LPS 刺激的 SH-SY5Y 细胞检查CISD2 和 PPAR- β在炎症信号传导中的作用。结果. WBM 减轻了 SCI 小鼠脊髓中 SCI 诱导的 CISD2、PPAR- β和IκB下调和胶质纤维酸性蛋白（GFAP；星形胶质细胞再激活标志物）的上调。此外，WBM (1  μ g/mL) 减轻了 LPS 诱导的 CISD2 下调。此外，具有 CISD2 敲低的 SH-SY5Y 神经细胞表现出 PPAR- β表达降低和 NF- κ B 信号传导增强。结论。据我们所知，这是第一项报告 CISD2 是 PPAR- β /NF- κ的上游调节剂的研究B 神经细胞中的促炎信号通路，并且 WBM 可以减轻 SCI 小鼠和 LPS 刺激的 ALT 星形胶质细胞中损伤诱导的 CISD2 下调。