Singh Gautam Avtar, Panda Ekta Swarnamayee, Balki Sneha, Pandey Shivam Kumar, Tiwari Aman, Singh Rakesh Kumar
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) - Raebareli. Transit campus, Bijnour-sisendi Road, Sarojini Nagar, Lucknow-226002, Uttar Pradesh, India.
Food Funct. 2025 Jan 20;16(2):731-749. doi: 10.1039/d4fo05278a.
: The aim of the current study was to study the therapeutic potential of chrysin against repeated intranasal amyloid-beta (Aβ)-induced interleukin-17 (IL-17) signaling in a mouse model of AD. : Male BALB/c mice were daily exposed to intranasal Aβ (10 μg/10 μL) for seven consecutive days. Chrysin was orally administered at doses of 25, 50 and 100 mg kg in 0.5% sodium carboxy methyl cellulose suspension from day 5 of Aβ administration for seven days. Following the treatment, the memory of the animals was appraised using Morris water maze, novel object recognition and passive avoidance tests. Further, the effects of chrysin on Aβ-induced IL-17 signaling and redox levels were evaluated in the cortex and hippocampus regions of the mouse brain through western blot and immunohistochemistry. : The exposure to Aβ through the intranasal route induced a significant decline in the spatial, learning and cognitive memory of the animals, and most interestingly, exposure to Aβ triggered IL-17-mediated signaling, which resulted in a significant increase in the expression of IL-17RA, Act1 and TRAF6. Furthermore, Aβ impaired the tissue redox level and inflammatory cytokines in the mouse brain. Alternatively, treatment with chrysin at 25, 50 and 100 mg kg oral doses alleviated Aβ-mediated memory decline, impaired redox levels and inflammation. Specifically, chrysin downregulated the expression of IL-17 and mediated signaling in the brain regions of the mice. : Chrysin was evidenced to be a potent antioxidant and anti-inflammatory agent, clearly showing a protective role against Aβ-induced IL-17-mediated inflammation in the brain of the mice.
本研究的目的是在阿尔茨海默病小鼠模型中，研究白杨素对反复经鼻给予淀粉样β蛋白（Aβ）诱导的白细胞介素-17（IL-17）信号传导的治疗潜力。雄性BALB/c小鼠连续7天每天经鼻给予Aβ（10μg/10μL）。从给予Aβ的第5天起，将白杨素以25、50和100mg/kg的剂量溶于0.5%羧甲基纤维素钠混悬液中口服给药7天。治疗后，使用莫里斯水迷宫、新物体识别和被动回避试验评估动物的记忆力。此外，通过蛋白质免疫印迹法和免疫组织化学法，评估白杨素对小鼠大脑皮质和海马区Aβ诱导的IL-17信号传导和氧化还原水平的影响。经鼻给予Aβ导致动物的空间、学习和认知记忆显著下降，最有趣的是，暴露于Aβ会触发IL-17介导的信号传导，导致IL-17RA、Act1和TRAF6的表达显著增加。此外，Aβ损害了小鼠大脑中的组织氧化还原水平和炎性细胞因子。另外，以25、50和100mg/kg口服剂量的白杨素治疗可减轻Aβ介导的记忆衰退、氧化还原水平受损和炎症。具体而言，白杨素下调了小鼠脑区中IL-17的表达并介导了信号传导。白杨素被证明是一种有效的抗氧化剂和抗炎剂，明显显示出对Aβ诱导的小鼠脑内IL-17介导的炎症具有保护作用。
