Department of Veterinary Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, 55200, Atakum, Samsun, Turkey.
Histochem Cell Biol. 2023 Nov;160(5):477-490. doi: 10.1007/s00418-023-02217-1. Epub 2023 Jun 28.
This study was conducted to demonstrate the possible protective and therapeutic effects of naringenin, an estrogenically effective flavonoid, in experimental autoimmune encephalomyelitis (EAE), which is the rodent model of multiple sclerosis. For this purpose, 50 12-week-old C57BL6 male mice were divided into five groups; control, naringenin, EAE, prophylactic naringenin + EAE, and EAE + therapeutic naringenin. The EAE model was induced with myelin oligodendrocyte glycoprotein, and naringenin (50 mg/kg) was administered by oral gavage. The prophylactic and therapeutic effects of naringenin were examined according to clinical, histopathological, immunohistochemical, electron microscopic, and RT-PCR (aromatase, 3βHSD, estrogen receptors, and progesterone receptor expression) parameters. The acute EAE model was successfully induced, along with its clinical and histopathological findings. RT-PCR showed that expression of aromatase, 3βHSD, estrogen receptor-β, and progesterone receptor gene decreased, while estrogen receptor-α increased after EAE induction. Electron microscopic analysis showed mitochondrial damage and degenerative changes in myelinated axons and neurons in EAE, which could be behind the downregulation in the expressions of neurosteroid enzymes. Aromatase immunopositivity rates also decreased in EAE, while estrogen receptor α and β, and progesterone receptor immunopositivity rates increased. Naringenin improved aromatase immunopositivity rates and gene expression in both prophylactic and therapeutic use. Clinical and histopathological findings revealed that EAE findings were alleviated in both prophylactic and therapeutic groups, along with significantly decreased inflammatory cell infiltrations in the white matter of the spinal cords. In conclusion, naringenin could provide long-term beneficial effects even in prophylactic use due to stimulating aromatase expression, but it could not prevent or eliminate the EAE model's lesions completely.
本研究旨在展示柚皮素（一种具有雌激素活性的类黄酮）在实验性自身免疫性脑脊髓炎（EAE）中的可能保护和治疗作用，EAE 是多发性硬化症的啮齿动物模型。为此，将 50 只 12 周龄的 C57BL6 雄性小鼠分为五组：对照组、柚皮素组、EAE 组、预防性柚皮素+EAE 组和 EAE+治疗性柚皮素组。用髓鞘少突胶质糖蛋白诱导 EAE 模型，通过口服灌胃给予柚皮素（50mg/kg）。根据临床、组织病理学、免疫组织化学、电子显微镜和 RT-PCR（芳香酶、3βHSD、雌激素受体和孕激素受体表达）参数，检查柚皮素的预防和治疗作用。成功诱导了急性 EAE 模型及其临床和组织病理学发现。RT-PCR 显示，EAE 诱导后，芳香酶、3βHSD、雌激素受体-β和孕激素受体基因的表达减少，而雌激素受体-α增加。电子显微镜分析显示，EAE 中髓鞘轴突和神经元的线粒体损伤和退行性变化可能是神经甾体酶表达下调的原因。EAE 中芳香酶免疫阳性率也降低，而雌激素受体 α 和 β 以及孕激素受体免疫阳性率增加。柚皮素可改善预防性和治疗性使用中的芳香酶免疫阳性率和基因表达。临床和组织病理学发现表明，预防性和治疗性组均缓解了 EAE 发现，脊髓白质中的炎症细胞浸润明显减少。总之，由于刺激芳香酶表达，柚皮素即使在预防性使用中也能提供长期的有益效果，但它不能完全预防或消除 EAE 模型的病变。
