Abstract
Neuroinflammation is a major factor in the pathogenesis of various neurodegenerative diseases. Microglia are resident macrophages that act as key mediators of inflammation in the brain. In response to inflammatory stimuli including lipopolysaccharide (LPS), microglial activation occurs immediately. Overproduction of inflammatory mediators released by activated microglia contributes to neuron damage in neurodegenerative disease. Therefore, identification of a compound that has anti-inflammatory activities and inhibits microglial activation may be an alternative therapeutic approach for the treatment of neurodegenerative diseases. Cyanidin-3-O-glucoside (C3G), a type of anthocyanin, possesses powerful anti-inflammatory activities. In this study, the anti-inflammatory effects of C3G were investigated in LPS-stimulated BV2 microglia. The results indicate that pretreatment with C3G significantly suppresses microglial activation and the production of neurotoxic mediators including nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6) in LPS-activated BV2 cells. Moreover, C3G downregulates the gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines via the suppression of NF-κB and p38 MAPK signaling pathways. Furthermore, a co-culture system to determine the indirect neuroprotective effects of C3G was used. Results demonstrated that conditioned medium (CM) from LPS-stimulated BV2 cells can promote the apoptosis of differentiated pheochromocytoma (PC12) cells through the activation of caspase-3, while C3G pretreatment in BV2 microglia can protect differentiated PC12 cells from microglial activation-induced apoptosis. Therefore, C3G may be a potential therapeutic agent for the treatment and prevention of neurodegenerative diseases associated with microglial activation.
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This study was funded by 50th Anniversary Chiang Mai University research fund for Chayanut Kaewmool (PHD/018/2557).
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Kaewmool, C., Udomruk, S., Phitak, T. et al. Cyanidin-3-O-Glucoside Protects PC12 Cells Against Neuronal Apoptosis Mediated by LPS-Stimulated BV2 Microglial Activation. Neurotox Res 37, 111–125 (2020). https://doi.org/10.1007/s12640-019-00102-1
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DOI: https://doi.org/10.1007/s12640-019-00102-1