Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006, Badajoz, Spain; Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Universidad de Extremadura, 06006, Badajoz, Spain.
Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006, Badajoz, Spain.
Food Chem Toxicol. 2022 Jun;164:113017. doi: 10.1016/j.fct.2022.113017. Epub 2022 Apr 19.
Kaempferol is a natural antioxidant present in vegetables and fruits used in human nutrition. In previous work, we showed that intraperitoneal (i.p.) kaempferol administration strongly protects against striatum neurodegeneration induced by i.p. injections of 3-nitropropionic acid (NPA), an animal model of Huntington's disease. Recently, we have shown that reactive A1 astrocytes generation is an early event in the neurodegeneration induced by NPA i.p. injections. In the present work, we have experimentally evaluated the hypothesis that kaempferol protects both against the activation of complement C3 protein and the generation of reactive A1 astrocytes in rat brain striatum and hippocampus. To this end, we have administered NPA and kaempferol i.p. injections to adult Wistar rats following the protocol described in previous work. Kaempferol administration prevents proteolytic activation of complement C3 protein and generation of reactive A1 astrocytes NPA-induced in the striatum and hippocampus. Also, it blocked the NPA-induced increase of NF-κB expression and enhanced secretion of cytokines IL-1α, TNFα, and C1q, which have been linked to the generation of reactive A1 astrocytes. In addition, kaempferol administration prevented the enhanced production of amyloid β peptides in the striatum and hippocampus, a novel finding in NPA-induced brain degeneration found in this work.
山柰酚是一种天然抗氧化剂,存在于蔬菜和水果中,用于人类营养。在之前的工作中,我们表明腹腔内(i.p.)给予山奈酚可以强烈保护腹腔内注射 3-硝基丙酸(NPA)引起的纹状体神经退行性变,NPA 是亨廷顿病的动物模型。最近,我们已经表明,反应性 A1 星形胶质细胞的产生是 NPA 腹腔内注射引起的神经退行性变的早期事件。在本工作中,我们通过实验评估了以下假设:山奈酚可以保护补体 C3 蛋白的激活和反应性 A1 星形胶质细胞在大鼠纹状体和海马中的生成。为此,我们按照之前工作中描述的方案,给成年 Wistar 大鼠腹腔内注射 NPA 和山奈酚。山奈酚的给予可防止补体 C3 蛋白的蛋白水解激活和 NPA 诱导的纹状体和海马中反应性 A1 星形胶质细胞的生成。此外,它还阻断了 NPA 诱导的 NF-κB 表达增加和细胞因子 IL-1α、TNFα 和 C1q 的分泌增加,这些因子与反应性 A1 星形胶质细胞的生成有关。此外,山奈酚的给予可防止纹状体和海马中淀粉样β肽的产生增加,这是在本工作中发现的 NPA 诱导的脑退化中的一个新发现。