Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Immunology Research Center, Department of Immunology and Allergy, Mashhad University of Medical Sciences, Mashhad, Iran.
Acta Neurobiol Exp (Wars). 2022;82(3):273-283. doi: 10.55782/ane-2022-026.
Multiple sclerosis (MS) is the most typical chronic inflammatory, autoimmune demyelinating disease of the central nervous system (CNS) which leads to physical dysfunction and paralysis in patients. A commonly used animal model for this disease is experimental autoimmune encephalomyelitis (EAE). Daphnetin (7,8‑dihydroxycoumarin) has been reported to exert various pharmacological activities, such as being neuroprotective and anti‑inflammatory, together with having antioxidant, anticancer, and antiviral properties. Eight‑week‑old C57BL/6 female mice were segregated into 3 groups, namely 1) a control group receiving PBS, 2) a low‑dose treatment group receiving 2 mg/kg of daphnetin, and, 3) a high‑dose treatment group receiving 8 mg/kg of daphnetin. EAE was induced with a subcutaneous injection of a combination of myelin oligodendrocyte glycoprotein (MOG) and complete Freund's adjuvant. On the day of induction, and again two days later, mice were injected intraperitoneally with pertussis toxin. Histological studies showed low lymphocyte infiltration and demyelination in the high and low dose treated groups. The ratio of spleen Treg cells and the levels of IL‑4, IL‑10, TGF‑β, and IL‑33 enhanced significantly in the treatment group related to the control group. Furthermore, both IL‑27 and IL‑35 were also enhanced significantly in the treatment group compared to the control group. Moreover, the levels of IFN‑γ, TNF‑α, and IL‑17 displayed a noticeable reduction in the daphnetin treated group. Daphnetin appears to improve the disease by increasing the expression of anti‑inflammatory cytokines and transcription factors (IL‑4, IL‑10, IL‑33, GATA3, TGF‑β, FoxP3), and reducing the production of pro‑inflammatory cytokines and transcription factors (IFN‑γ, STAT4, T‑bet, IL‑17, STAT3, ROR‑γt, TNF‑α).
多发性硬化症（MS）是中枢神经系统（CNS）最典型的慢性炎症性、自身免疫性脱髓鞘疾病，导致患者身体机能障碍和瘫痪。实验性自身免疫性脑脊髓炎（EAE）是该疾病的常用动物模型。香豆素（7,8-二羟基香豆素）已被报道具有多种药理活性，如神经保护和抗炎作用，同时具有抗氧化、抗癌和抗病毒特性。将 8 周龄的 C57BL/6 雌性小鼠分为 3 组，即 1）对照组给予 PBS，2）低剂量治疗组给予 2mg/kg 的香豆素，和 3）高剂量治疗组给予 8mg/kg 的香豆素。通过髓鞘少突胶质细胞糖蛋白（MOG）和完全弗氏佐剂的皮下注射诱导 EAE。在诱导的当天，以及两天后，再次通过腹腔内注射百日咳毒素。组织学研究显示，高剂量和低剂量治疗组的淋巴细胞浸润和脱髓鞘程度较低。与对照组相比，治疗组的脾 Treg 细胞比例以及 IL-4、IL-10、TGF-β 和 IL-33 的水平显著升高。此外，与对照组相比，治疗组的 IL-27 和 IL-35 水平也显著升高。此外，在香豆素治疗组中，IFN-γ、TNF-α 和 IL-17 的水平明显降低。香豆素通过增加抗炎细胞因子和转录因子（IL-4、IL-10、IL-33、GATA3、TGF-β、FoxP3）的表达，并减少促炎细胞因子和转录因子（IFN-γ、STAT4、T-bet、IL-17、STAT3、ROR-γt、TNF-α）的产生，从而改善疾病。
