Maalouly Georges, Saliba Youakim, Hajal Joelle, Zein-El-Din Anna, Fakhoury Luana, Najem Rouaa, Smayra Viviane, Nassereddine Hussein, Fares Nassim
Laboratory of Research in Physiology and Pathophysiology, Faculty of Medicine, Saint Joseph University of Beirut, Beirut 1104 2020, Lebanon.
Faculty of Medicine, Saint Joseph University of Beirut, Beirut 1104 2020, Lebanon.
Nutrients. 2025 May 27;17(11):1820. doi: 10.3390/nu17111820.
The pathogenesis of neuropsychiatric lupus erythematosus (NPSLE) is very complex and is associated with neuroinflammation and blood-brain barrier compromise. Experimental investigations of NPSLE have classically relied on spontaneous models. Recently, TLR7 agonist-induced lupus has been shown to exhibit similar neuropsychiatric manifestations to spontaneous ones. Cinnamon is a widespread spice and natural flavoring agent. It has been proven to modulate vascular endothelial tight junctions, neuroinflammation, and autoimmunity pathways, but it has never been tested in relation to lupus. In this pilot study, we aimed to explore the disease-modifying effect of on NPSLE in a TLR7 agonist-induced model. An experimental design was followed in this study. Lupus was induced in C57BL/6J female mice via the direct application of imiquimod, a TLR7 agonist (5% imiquimod cream, 1.25 mg three times weekly), to the skin. Mice were divided into five groups ( = 8 per group): a sham group (S), a sham group supplemented with cinnamon (SC), an imiquimod-treated group (L), an imiquimod-treated group supplemented with cinnamon starting from induction (LC), and an imiquimod-treated group supplemented with cinnamon beginning two weeks prior to induction (CLC). This protocol was followed for six consecutive weeks. powder was administered orally at 200 mg/kg, 5 days per week. Behavioral alterations were significantly ameliorated in the CLC group compared to lupus mice. Neuronal shrinkage and nuclear chromatin condensation were visible in the hippocampal cornu ammonis and dentate gyrus zones of lupus mice, with an increased expression of TLR7 and NLRP3, versus significantly less neurodegeneration and TLR7 and NLRP3 expression in the CLC group. In addition, the expression of the blood-brain barrier endothelial cell tight junction proteins claudin-1, occludin, and ZO-1 was abnormally modified in lupus mice and was restored in the CLC group. Moreover, while the cell-cell border delocalization of claudin-1 was documented in cultured blood-brain barrier endothelial cells treated with the plasma of lupus mice to a punctate intracytoplasmic fluorescence pattern, only cells treated with the plasma of the CLC group exhibited a complete reversal of this redistribution of claudin-1. Finally, cinnamaldehyde seemed to interact with TLR7 at multiple sites. seems to alleviate the pathogenesis of NPSLE. Supplementation with could be of great interest to modulate the activity and severity of the disease.
神经精神性狼疮（NPSLE）的发病机制非常复杂，与神经炎症和血脑屏障受损有关。NPSLE的实验研究传统上依赖于自发模型。最近，已证明Toll样受体7（TLR7）激动剂诱导的狼疮表现出与自发狼疮相似的神经精神症状。肉桂是一种广泛使用的香料和天然调味剂。已证实它可调节血管内皮紧密连接、神经炎症和自身免疫途径，但从未针对狼疮进行过测试。在这项初步研究中，我们旨在探讨其对TLR7激动剂诱导模型中NPSLE的疾病修饰作用。本研究遵循实验设计。通过直接在C57BL/6J雌性小鼠皮肤上涂抹咪喹莫特（一种TLR7激动剂，5%咪喹莫特乳膏，每周三次，每次1.25毫克）诱导狼疮。将小鼠分为五组（每组n = 8）：假手术组（S）、补充肉桂的假手术组（SC）、咪喹莫特治疗组（L）、从诱导开始补充肉桂的咪喹莫特治疗组（LC）以及在诱导前两周开始补充肉桂的咪喹莫特治疗组（CLC）。该方案连续遵循六周。肉桂粉以200毫克/千克的剂量口服给药，每周5天。与狼疮小鼠相比，CLC组的行为改变得到显著改善。在狼疮小鼠的海马角回和齿状回区域可见神经元萎缩和核染色质浓缩，TLR7和NLRP3表达增加，而CLC组的神经退行性变以及TLR7和NLRP3表达明显较少。此外，血脑屏障内皮细胞紧密连接蛋白claudin-1、闭合蛋白和闭锁小带蛋白-1（ZO-1）的表达在狼疮小鼠中发生异常改变，而在CLC组中恢复正常。此外，在用狼疮小鼠血浆处理的培养血脑屏障内皮细胞中，claudin-1的细胞间边界发生错位，呈现点状胞浆内荧光模式，而只有用CLC组血浆处理的细胞表现出claudin-1这种重新分布的完全逆转。最后，肉桂醛似乎在多个位点与TLR7相互作用。肉桂似乎可以减轻NPSLE的发病机制。补充肉桂可能对调节该疾病的活动和严重程度具有重要意义。
