Modulation of Adenosine Receptors by Hops and Xanthohumol in Cell Cultures

Abstract

Adenosine receptors (ARs) have been involved in neurodegenerative diseases such as Alzheimer disease, where oxidative stress contributes to neurodegeneration and cell death. Therefore, there is increasing interest in developing antioxidative strategies to avoid or reduce neurodegeneration. We have previously described that different beer extracts modulate ARs and protect glioma and neuroblastoma cells from oxidative stress. The present work aimed to analyze the possible protective effect of hops (Humulus lupulus L.), a major component of beer, and xanthohumol on cell death elicited by oxidative stress and their modulation of ARs in rat C6 glioma and human SH-SY5Y neuroblastoma cells. Different extraction methods were employed in two hops varieties (Nugget and Columbus). Cell viability was determined by the XTT method in cells exposed to these hops extracts and xanthohumol. ARs were analyzed by radioligand binding and real-time PCR assays. Hops extract reverted the cell death observed under oxidative stress and modulated adenosine A 1 and A 2 receptors in both cell types. Xanthohumol was unable to revert the effect of oxidative stress in cell viability but it also modulated ARs similarly to hops. Therefore, healthy effects of beer described previously could be due, at least in part, to their content of hops and the modulation of ARs.

Effect of Xanthohumol, a Bioactive Natural Compound from Hops, on Adenosine Pathway in Rat C6 Glioma and Human SH-SY5Y Neuroblastoma Cell Lines

“…First, a study of the cell viability of C6 and SH-SY5Y cells in the presence of different concentrations of Xn was conducted in order to establish a proper concentration that has no severe toxicity to these cell lines. Previous results of our group showed no significant effect of 10 µM Xn in these cell lines; therefore, 5 and 15 µM Xn were tested [ 28 ]. Results presented in Figure 1 show a significant decrease in cell viability when both C6 and SH-SY5Y cells were exposed to 15 µM of Xn (C6: 100.0 ± 3.9 vs. 65.8 ± 3.1%, * p < 0.05; SH-SY5Y: 100.0 ± 4.7 vs. 77.8 ± 5.1%, * p < 0.05.…”

“…The search for possible natural bioactive compounds that modulate the functionality of adenosine receptors could, therefore, be very helpful in the prevention and identification of new therapeutic molecules for AD. In that sense, previous work carried out in our group has shown that Xn causes a modulation at the level of gene expression of adenosine receptors in SH-SY5Y cells [ 28 ]. However, until now, it has not been fully reported how it could affect the adenosinergic pathway, including levels of these receptors in the membrane, functionality, or related enzymatic activities.…”

Resveratrol enhances A1 and hinders A2A adenosine receptors signaling in both HeLa and SH-SY5Y cells: Potential mechanism of its antitumoral action

“…Therefore, the present study examined the possible involvement of adenosinergic signaling in the antitumoral action of RSV in human HeLa cervical carcinoma cells, as non-neural origin cells, and SH-SY5Y neuroblastoma cells, as a model of a neuronal-like cell. Ee have previously reported some regulatory mechanisms of adenosine receptors in both cell lines (42,43). desired concentration.…”