Sulfasalazine（柳氮磺吡啶，AbMole，M2197）是一种铁死亡（Ferroptosis）诱导剂，可通过抑制胱氨酸/谷氨酸逆向转运体（System Xc-）诱导铁死亡。研究表明，Sulfasalazine（CAS No.：599-79-1）通过阻断System Xc-功能，抑制细胞内胱氨酸摄取，导致谷胱甘肽（GSH）合成受阻，进而降低谷胱甘肽过氧化物酶4（GPX4）活性，引发脂质过氧化积累和铁依赖性细胞死亡[1]。此外，Sulfasalazine（Salazopyrin）还可通过下调ERK1/2和上调P53促进铁死亡[2]，并表现出对NF-κB通路的抑制活性[3]。在细胞模型中，Sulfasalazine的作用已被广泛验证。例如，在类风湿关节炎成纤维样滑膜细胞（FLSs）中，Sulfasalazine通过降低GPX4和SLC7A11表达促进铁死亡[2]。在BV2小胶质细胞中，Sulfasalazine能抑制葡萄糖剥夺诱导的炎症反应，促进M1型小胶质细胞向M2型的极化，并通过调节STING/NF-κB通路发挥保护作用[4]。此外，Sulfasalazine在RAW264.7巨噬细胞和HT-29结肠上皮细胞中能有效调节炎症因子（如IL-6、TNF-α）和紧密连接蛋白的表达[5]。动物实验方面，Sulfasalazine（AbMole，M2197）在多种疾病模型中显示出调控潜力。Sulfasalazine（NSC 667219）在C57BL/6小鼠的缺血性脑卒中（MCAO）模型中，被证实可缩小梗死面积、恢复脑血流并改善运动功能，其机制与抑制神经炎症相关[4]。Sulfasalazine（Sulphasalazine）在Balb/c或C57BL/6小鼠的结肠炎模型（DSS诱导）中，能有效减轻肠道炎症，并降低髓过氧化物酶（MPO）活性和促炎因子（IL-1β、TNF-α）水平[6]。此外，Sulfasalazine在BALB/c小鼠的胶原抗体诱导关节炎（CAIA）模型中，表现出与糖皮质激素Prednisolone相当的抗炎效果[7]。

参考文献及鸣谢

[1] Kim, E. H.; Shin, D.; Lee, J.; et al. CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer. Cancer letters 2018, 432, 180-190.

[2] Zhao, C.; Yu, Y.; Yin, G.; et al. Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis. Inflammopharmacology 2024, 32 (2), 1277-1294.

[3] Han, J.; Zhan, L. N.; Huang, Y.; et al. Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-kappaB p65/GPX4 signaling pathway. Scientific reports 2024, 14 (1), 5078.

[4] Li, X.; Ding, H.; Jing, J.; et al. Sulfasalazine improves neuronal function in mice with ischemic stroke by inhibiting the STING/NF-kappaB pathway. Naunyn-Schmiedeberg's archives of pharmacology 2025, 398 (5), 5797-5810.

[5] Qiang, X.; Liang, S.; Lv, Y.; et al. Advanced glycation end products (AGEs) impair the intestinal epithelial barrier via STAT3 activation mediated by macrophages. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2024, 192, 114966.

[6] Shin, M. R.; Park, H. J.; Seo, B. I.; et al. New approach of medicinal herbs and sulfasalazine mixture on ulcerative colitis induced by dextran sodium sulfate. World journal of gastroenterology 2020, 26 (35), 5272-5286.

[7] Sim, J. H.; Lee, W. K.; Lee, Y. S.; et al. Assessment of collagen antibody-induced arthritis in BALB/c mice using bioimaging analysis and histopathological examination. Laboratory animal research 2016, 32 (3), 135-143.