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Microglial HO‐1 induction by curcumin provides antioxidant, antineuroinflammatory, and glioprotective effects
Author(s) -
Parada Esther,
Buendia Izaskun,
Navarro Elisa,
Avendaño Carlos,
Egea Javier,
López Manuela G.
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500279
Subject(s) - curcumin , proinflammatory cytokine , microglia , oxidative stress , pharmacology , neurodegeneration , chemistry , reactive oxygen species , astrocyte , tumor necrosis factor alpha , neuroglia , rotenone , inflammation , biology , biochemistry , immunology , mitochondrion , medicine , neuroscience , pathology , central nervous system , disease
Scope We have studied if curcumin can protect glial cells under an oxidative stress and inflammatory environment, which is known to be deleterious in neurodegeneration. Methods and results Primary rat glial cultures exposed to the combination of an oxidative (rotenone/oligomycin A) and a proinflammatory LPS stimuli reduced by 50% glial viability. Under these experimental conditions, curcumin afforded significant glial protection and reduction of reactive oxygen species; these effects were blocked by the HO‐1 inhibitor tin protoporphyrin‐IX (SnPP). These findings correlate with the observation that curcumin induced the antioxidative protein HO‐1. Most interesting was the observation that the glial protective effects related to HO‐1 induction were microglial specific as shown in glial cultures from LysM Cre Hmox ∆/∆ mice where curcumin lost its protective effect. Under LPS conditions, curcumin reduced the microglial proinflammatory markers iNOS and tumor necrosis factor, but increased the anti‐inflammatory cytokine IL4. Analysis of the microglial phenotype showed that curcumin favored a ramified morphology toward a microglial alternative activated state against LPS insult also by a HO‐1‐dependent mechanism. Conclusion The curry constituent curcumin protects glial cells and promotes a microglial anti‐inflammatory phenotype by a mechanism that implicates HO‐1 induction; these effects may have impact on brain protection under oxidative and inflammatory conditions.