Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, China.
Department of endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Phytother Res. 2024 Jul;38(7):3337-3351. doi: 10.1002/ptr.8205. Epub 2024 Apr 18.
The discovery of alternative medicines with fewer adverse effects is urgently needed for rheumatoid arthritis (RA). Sophoridine (SR), the naturally occurring quinolizidine alkaloid isolated from the leguminous sophora species, has been demonstrated to possess a wide range of pharmacological activities. However, the effect of SR on RA remains unknown. In this study, the collagen-induced arthritis (CIA) rat model and tumor necrosis factor alpha (TNFα)-induced fibroblast-like synoviocytes (FLSs) were utilized to investigate the inhibitory effect of SR on RA. The anti-arthritic effect of SR was evaluated using the CIA rat model in vivo and TNFα-stimulated FLSs in vitro. Mechanistically, potential therapeutic targets and pathways of SR in RA were analyzed through drug target databases and disease databases, and validation was carried out through immunofluorescence, immunohistochemistry, and Western blot. The in vivo results revealed that SR treatment effectively ameliorated synovial inflammation and bone erosion in rats with CIA. The in vitro studies showed that SR could significantly suppress the proliferation and migration in TNFα-induced arthritic FLSs. Mechanistically, SR treatment efficiently inhibited the activation of MAPKs (JNK and p38) and NF-κB pathways in TNFα-induced arthritic FLSs. These findings were further substantiated by Immunohistochemistry results in the CIA rat. SR exerts an anti-arthritic effect in CIA rats through inhibition of the pathogenic characteristic of arthritic FLSs via suppressing NF-κB and MAPKs (JNK and p38) signaling pathways. SR may have a great potential for development as a novel therapeutic agent for RA treatment.
治疗类风湿关节炎（RA），急需发现具有更少副作用的替代药物。槐定碱（SR）是从豆科槐属植物中分离出来的天然喹诺里西啶生物碱，已被证明具有广泛的药理活性。然而，SR 对 RA 的作用尚不清楚。本研究利用胶原诱导性关节炎（CIA）大鼠模型和肿瘤坏死因子-α（TNFα）诱导的成纤维样滑膜细胞（FLSs）来研究 SR 对 RA 的抑制作用。采用 CIA 大鼠模型体内和 TNFα 刺激的 FLSs 体外来评估 SR 的抗关节炎作用。通过药物靶标数据库和疾病数据库分析 SR 在 RA 中的潜在治疗靶点和途径，并通过免疫荧光、免疫组化和 Western blot 进行验证。体内结果表明，SR 治疗可有效改善 CIA 大鼠的滑膜炎症和骨侵蚀。体外研究表明，SR 可显著抑制 TNFα 诱导的关节炎 FLSs 的增殖和迁移。机制上，SR 处理可有效抑制 TNFα 诱导的关节炎 FLSs 中 MAPKs（JNK 和 p38）和 NF-κB 通路的激活。这些发现通过 CIA 大鼠中的免疫组化结果得到进一步证实。SR 通过抑制 NF-κB 和 MAPKs（JNK 和 p38）信号通路抑制关节炎 FLSs 的致病特征，在 CIA 大鼠中发挥抗关节炎作用。SR 可能具有作为治疗 RA 的新型治疗剂的巨大潜力。
