Anhydroexfoliamycin, a Streptomyces Secondary Metabolite, Mitigates Microglia-Driven Inflammation

Abstract

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