期刊
CELLULAR AND MOLECULAR NEUROBIOLOGY
卷 40, 期 4, 页码 603-615出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-019-00758-5
关键词
Microglia; Lipopolysaccharide; Cyclophilin A; Inflammation; Gracilins
资金
- Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia [2017 GRC GI-1682] Funding Source: Medline
- European Commission [0161-Nanoeaters -1-E-1, Interreg Agritox EAPA-998-2018, Interreg AlertoxNet EAPA-317-2016] Funding Source: Medline
- Horizon 2020 [778069-EMERTOX] Funding Source: Medline
- Ministerio de Economía, Industria y Competitividad, Gobierno de España [AGL2016-78728-R, ISCIII/PI16/01830, ITC-20161072, RTC-2016-5507-2] Funding Source: Medline
Gracilins are diterpenes derivative, isolated from the marine sponge Spongionella gracilis. Natural gracilins and synthetic derivatives have shown antioxidant, immunosuppressive, and neuroprotective capacities related to the affinity for cyclophilins. The aim of this work was to study anti-inflammatory and immunosuppressive pathways modulated by gracilin L and two synthetic analogues, compound 1 and 2, on a cellular model of inflammation. In this way, the murine BV2 microglia cell line was used. To carry out the experiments, microglia cells were pre-treated with compounds for 1 h and then stimulated with lipopolysaccharide for 24 h to determine reactive oxygen species production, mitochondrial membrane potential, the release of nitric oxide, interleukin-6 and tumor necrosis factor-alpha and the expression of Nuclear factor-erythroid 2-related factor 2, Nuclear Factor-kappa B, the inducible nitric oxide synthase, and the cyclophilin A. Finally, a co-culture of neuron SH-SY5Y and microglia BV2 cells was used to check the neuroprotective effect of these compounds. Cyclosporine A was used as a control of effect. The compounds were able to decrease inflammatory mediators, the expression of inflammatory target proteins as well as they activated anti-oxidative mechanism upon inflammatory conditions. For this reason, natural and synthetic gracilins could be interesting for developing anti-inflammatory drugs.
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