Punicalagin inhibits neuron ferroptosis and secondary neuroinflammation to promote spinal cord injury recovery.

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-01-16 DOI:10.1016/j.intimp.2025.114048

Wei Wang, Lichen Zhang, Xin Liu, Qiangqiang Guo, Xinzhao Jiang, Jie Wu, Yiwei Zhu, Yong Gu, Liang Chen, Kun Xi

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Abstract

Spinal cord injury (SCI) represents a severe type of central nervous system damage, with no effective treatment currently available, partly due to neuronal ferroptosis and subsequent neuroinflammation. Punicalagin, an anti-inflammatory compound extracted from pomegranate peel, has exhibited therapeutic potential for inflammatory diseases. In this study, we present evidence that punicalagin facilitates the recovery of neurological function following SCI by mitigating neuronal ferroptosis. Mechanistically, this effect involves the upregulation of nuclear factor E2-related factor 2 (Nrf2) and the activation of the Nrf2- Solute Carrier Family 7 Member 11 (SLC7A11)- Glutathione Peroxidase 4 (GPX4) signaling pathway. Furthermore, punicalagin aids in the resolution of secondary neuroinflammation by modulating the M1/M2 polarization of microglia, thereby promoting SCI recovery. Collectively, these findings suggest that punicalagin enhances functional recovery after SCI by inhibiting neuronal ferroptosis and reducing microglial M1 polarization. Consequently, punicalagin may represent a promising therapeutic agent for the treatment of spinal cord injury.

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甘草多糖抑制神经元铁下垂和继发性神经炎症，促进脊髓损伤恢复。

脊髓损伤（SCI）是一种严重的中枢神经系统损伤，目前尚无有效的治疗方法，部分原因是神经元铁下垂和随后的神经炎症。从石榴皮中提取的一种抗炎化合物石榴苷已显示出治疗炎症性疾病的潜力。在这项研究中，我们提出的证据表明，punicalagin通过减轻神经元下垂，促进脊髓损伤后神经功能的恢复。在机制上，这种作用涉及核因子e2相关因子2 （Nrf2）的上调和Nrf2-可溶性载体家族7成员11 (SLC7A11)-谷胱甘肽过氧化物酶4 （GPX4）信号通路的激活。此外，槟榔苷通过调节小胶质细胞的M1/M2极化来帮助解决继发性神经炎症，从而促进脊髓损伤的恢复。综上所述，这些发现表明，punicalagin通过抑制神经元铁下垂和减少小胶质M1极化来促进脊髓损伤后的功能恢复。因此，槟榔苷可能是一种很有前途的治疗脊髓损伤的药物。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.