Anhydroexfoliamycin, a Streptomyces Secondary Metabolite, Mitigates Microglia-Driven Inflammation
| العنوان: | Anhydroexfoliamycin, a Streptomyces Secondary Metabolite, Mitigates Microglia-Driven Inflammation |
|---|---|
| المؤلفون: | Luis M. Botana, Rebeca Alvariño, Amparo Alfonso, Nadia Pérez-Fuentes, Sandra Gegunde |
| المساهمون: | Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica |
| المصدر: | Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname |
| بيانات النشر: | ACS Publications, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Physiology, Cognitive Neuroscience, Metabolite, Inflammation, Biochemistry, Neuroprotection, Proinflammatory cytokine, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Neuroinflammation, 030304 developmental biology, 0303 health sciences, Microglia, biology, Chemistry, Cell Biology, General Medicine, Neuron, Streptomyces, 3. Good health, Cell biology, Nitric oxide synthase, medicine.anatomical_structure, biology.protein, medicine.symptom, Antioxidant, 030217 neurology & neurosurgery |
| الوصف: | Anhydroexfoliamycin, a secondary metabolite from Streptomyces, has shown antioxidant properties in primary cortical neurons reducing neurodegenerative hallmarks diseases, both in vitro and in vivo models. Activated microglia, in the central nervous system, plays a crucial role in neuroinflammation and is associated with neurodegeneration. Therefore, the aim of the present study was to determine the anti-inflammatory and antioxidant potential of the anhydroexfoliamycin over microglia BV2 cells. Neuroinflammation was simulated by incubation of microglia cells in the presence of lipopolysaccharide to activate proinflammatory transduction pathways. Moreover, a coculture of neuron SH-SY5Y and microglia BV2 cells was used to evaluate the neuroprotective properties of the Streptomyces metabolite. When microglia cells were preincubated with anhydroexfoliamycin, proinflammatory pathways, such as the translocation of the nuclear factor κB, the phosphorylation of c-Jun N-terminal kinase, and the inducible nitric oxide synthase expression, were inhibited. In addition, intracellular reactive oxygen species generation and the liberation of nitric oxide, interleukin 6, and tumor necrosis factor α were also decreased. Besides, the Streptomyces-derived compound showed antioxidant properties promoting the translocation of the factor erythroid 2-related factor 2 and protecting the SH-SY5Y cells from the neurotoxic mediators released by activated microglia. The effects of this compound were at the same level as the immunosuppressive drug cyclosporine A. Therefore, these results indicate that anhydroexfoliamycin is a promising tool to control microglia-driven inflammation with therapeutic potential in neuroinflammation The research leading to these results has received funding from the following FEDER cofunded grants: Conselleria de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (Grant ED431C 2017/01); Ministerio de Ciencia e Innovación Grants ISCIII/PI16/01830 and ISCIII/PI19/01248; European Union Interreg AlertoxNet Grant EAPA-317-2016, Interreg Agritox Grant EAPA-998-2018, and Grant H2020 778069-EMERTOX. S.G. was supported by a fellowship from FIDIS, Spain SI |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::23e8a0d02ebbcbedfdf5dd5fabd18069Test http://hdl.handle.net/10347/29210Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....23e8a0d02ebbcbedfdf5dd5fabd18069 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |