Journal
TOXINS
Volume 15, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/toxins15010047
Keywords
1,4-naphthoquinones; Ca2+ influx; YO-PRO-1 uptake; P2X7R; macrophages; ROS production; IL-1 beta and TNF-alpha release; COX-2 activity; antioxidant activity; inflammation
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In this study, 1,4-naphthoquinone thioglucoside derivatives U-286 and U-548 were found to inhibit inflammation induced by ATP/LPS via P2X7 receptors. These compounds were able to inhibit calcium influx and reactive oxygen species production, and showed antioxidant activity in mouse brain homogenate. They also decreased COX-2 enzyme activity, reduced the release of pro-inflammatory cytokines, and protected macrophage cells against the toxic effects of ATP and LPS.
P2X7 receptors are ligand-gated ion channels activated by ATP and play a significant role in cellular immunity. These receptors are considered as a potential therapeutic target for the treatment of multiple inflammatory diseases. In the present work, using spectrofluorimetry, spectrophotometry, Western blotting and ELISA approaches, the ability of 1,4-naphthoquinone thioglucoside derivatives, compounds U-286 and U-548, to inhibit inflammation induced by ATP/LPS in RAW 264.7 cells via P2X7 receptors was demonstrated. It has been established that the selected compounds were able to inhibit ATP-induced calcium influx and the production of reactive oxygen species, and they also exhibited pronounced antioxidant activity in mouse brain homogenate. In addition, compounds U-286 and U-548 decreased the LPS-induced activity of the COX-2 enzyme, the release of pro-inflammatory cytokines TNF-alpha and IL-1 beta in RAW 264.7 cells, and significantly protected macrophage cells against the toxic effects of ATP and LPS. This study highlights the use of 1,4-naphthoquinones as promising purinergic P2X7 receptor antagonists with anti-inflammatory activity. Based on the data obtained, studied synthetic 1,4-NQs can be considered as potential scaffolds for the development of new anti-inflammatory and analgesic drugs.
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