PDF(Pubmed)
Abstract：
Xanthohumol (Xn) is an antioxidant flavonoid mainly extracted from hops (Humulus lupulus), one of the main ingredients of beer. As with other bioactive compounds, their therapeutic potential against different diseases has been tested, one of which is Alzheimer\'s disease (AD). Adenosine is a neuromodulatory nucleoside that acts through four different G protein-coupled receptors: A1 and A3, which inhibit the adenylyl cyclases (AC) pathway, and A2A and A2B, which stimulate this activity, causing either a decrease or an increase, respectively, in the release of excitatory neurotransmitters such as glutamate. This adenosinergic pathway, which is altered in AD, could be involved in the excitotoxicity process. Therefore, the aim of this work is to describe the effect of Xn on the adenosinergic pathway using cell lines. For this purpose, two different cellular models, rat glioma C6 and human neuroblastoma SH-SY5Y, were exposed to a non-cytotoxic 10 µM Xn concentration. Adenosine A1 and A2A, receptor levels, and activities related to the adenosine pathway, such as adenylate cyclase, protein kinase A, and 5\'-nucleotidase, were analyzed. The adenosine A1 receptor was significantly increased after Xn exposure, while no changes in A2A receptor membrane levels or AC activity were reported. Regarding 5\'-nucleotidases, modulation of their activity by Xn was noted since CD73, the extracellular membrane attached to 5\'-nucleotidase, was significantly decreased in the C6 cell line. In conclusion, here we describe a novel pathway in which the bioactive flavonoid Xn could have potentially beneficial effects on AD as it increases membrane A1 receptors while modulating enzymes related to the adenosine pathway in cell cultures.
摘要：
Xanthohumol（Xn）是一种抗氧化剂类黄酮，主要从啤酒花（Humuluslupulus）中提取，啤酒的主要成分之一。和其他生物活性化合物一样，他们对不同疾病的治疗潜力已经过测试，其中之一是阿尔茨海默病（AD）。腺苷是一种神经调节核苷，通过四种不同的G蛋白偶联受体起作用：A1和A3，它们抑制腺苷酸环化酶（AC）途径，A2A和A2B，刺激这种活动，导致减少或增加，分别,释放兴奋性神经递质，如谷氨酸。这个腺苷碱能途径，在AD中被改变，可能参与了兴奋毒性过程。因此,这项工作的目的是使用细胞系描述Xn对腺苷途径的影响。为此,两种不同的细胞模型,大鼠神经胶质瘤C6和人神经母细胞瘤SH-SY5Y，暴露于非细胞毒性10μMXn浓度。腺苷A1和A2A，受体水平，以及与腺苷途径相关的活性，如腺苷酸环化酶，蛋白激酶A,和5'-核苷酸酶，进行了分析。Xn暴露后腺苷A1受体显著增加，而A2A受体膜水平或AC活性没有变化的报道。关于5'-核苷酸酶，由于CD73，细胞外膜附着于5'-核苷酸酶，在C6细胞系中显著降低。总之,在这里，我们描述了一种新的途径，其中生物活性类黄酮Xn可能对AD产生潜在的有益作用，因为它增加了膜A1受体，同时调节细胞培养物中与腺苷途径相关的酶。
