Department of Biochemistry, Faculty of Veterinary Medicine, Ondokuz Mayis University, Atakum, 55200 Samsun, Turkey.
Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayis University, Atakum, 55200 Samsun, Turkey.
Fitoterapia. 2022 Jan;156:105099. doi: 10.1016/j.fitote.2021.105099. Epub 2021 Dec 9.
The aim of this study is to investigate the potential preventive and therapeutic effects of nobiletin by evaluating the expression of cytokines associated with inflammatory reactions in an autoimmune encephalomyelitis mouse model. A total of 60 male C57BL/6 mice aged between 8 and 10 weeks were used. Mice were divided into six groups (n = 10 mice per group): control, EAE, low-prophylaxis, high-prophylaxis, low-treatment and high-treatment. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG) and pertussis toxin. Nobiletin was administered in low (25 mg/kg) and high (50 mg/kg) doses, intraperitoneally. The prophylactic and therapeutic effects of nobiletin on brain tissue and spinal cord were evaluated by expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), IL-6, IL-10 and transforming growth factor-beta (TGF-β) using immunohistochemistry and real-time polymerase chain reaction (RT-PCR). Prophylactic and therapeutic use of nobiletin inhibited EAE-induced increase of TNF-α, IL-1β and IL-6 activities to alleviate inflammatory response in brain and spinal cord. Moreover, nobiletin supplement dramatically increased the IL-10, TGF-β and IFNγ expressions in prophylaxis and treatment groups compared with the EAE group in the brain and spinal cord. The results obtained from this study show that prophylactic and therapeutic nobiletin modulates expressions of proinflammatory and antiinflammatory cytokines in brain and spinal cord dose-dependent manner in EAE model. These data demonstrates that nobiletin has a potential to attenuate inflammation in EAE mouse model. These experimental findings need to be supported by clinical studies.
本研究旨在通过评估与炎症反应相关的细胞因子在自身免疫性脑脊髓炎（EAE）小鼠模型中的表达，来研究诺必行对炎症反应的潜在预防和治疗作用。共使用 60 只 8-10 周龄雄性 C57BL/6 小鼠。将小鼠分为六组（每组 10 只）：对照组、EAE 组、低预防组、高预防组、低治疗组和高治疗组。通过髓鞘少突胶质细胞糖蛋白（MOG）和百日咳毒素诱导实验性自身免疫性脑脊髓炎（EAE）。通过腹腔内给予低（25mg/kg）和高（50mg/kg）剂量的诺必行。通过免疫组织化学和实时聚合酶链反应（RT-PCR）评估诺必行对脑组织和脊髓的预防和治疗作用，检测白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFNγ）、IL-6、IL-10 和转化生长因子-β（TGF-β）的表达。诺必行的预防和治疗作用可抑制 EAE 诱导的 TNF-α、IL-1β 和 IL-6 活性增加，从而减轻脑和脊髓的炎症反应。此外，与 EAE 组相比，在预防和治疗组中，诺必行补充剂可显著增加大脑和脊髓中 IL-10、TGF-β 和 IFNγ 的表达。本研究结果表明，诺必行在 EAE 模型中以剂量依赖的方式调节大脑和脊髓中促炎和抗炎细胞因子的表达。这些数据表明，诺必行具有减轻 EAE 小鼠模型中炎症的潜力。这些实验结果需要通过临床研究来支持。
