Effects of piperine on lipopolysaccharide-induced injuries and oxidative changes in rat brain glial cell cultures

Abstract

Oxidative stress plays a role in the aging process and is one of the pathogenic causes in a variety of neurodegenerative disorders. In this study, effects of piperine on lipopolysaccharide (LPS)-induced injuries and oxidative changes in cultured glial cells from rat brains were investigated. Treatment of cultured glial cells with piperine displayed bimodal effects. At low concentrations (1-10 micro-M), it significantly increased mitochondrial metabolic activity after 12 and 24 hr of incubation with no apparent effects on cell survival. In contrast, mitochondrial activity and the number of surviving glial cells were markedly decreased at higher concentrations of piperine (25-100 micro-M) after 6, 12 and 24 hr of incubation. After an exposure to 0.01-100 microgram/ml of LPS for 96 hr, mitochondrial metabolic activity of glial cells was decreased by approximately 20-30% without significant effects on cell viability. Treatment with 1-10 micro-M of piperine or 100 micro-M of trolox for 24 hr before exposure to 1 microgram/ml of LPS for 96 hr and treatment with 5 and 7.5 micro-M of piperine or 100 micro-M of trolox for 24 hr after exposure to 1 microgram/ml of LPS for 96 hr significantly boosted up mitochondrial activity of LPS-exposed glial cells. Under the same condition, the number of cell survived was unaffected. Treatment with 7.5 and 10 micro-M of piperine during exposure to 1 microgram/ml of LPS for 96 hr did not affect mitochondrial metabolic activity and the number of surviving glial cells when compared with LPS-treated group. While incubation with 1 microgram/ml of LPS for 24 hr had no effect on mitochondrial metabolic activity and cell viability. However, mitochondrial activity was significantly increased after treatment with 10 micro-M of piperine or 100 micro-M of trolox during exposure to 1 microgram/ml of LPS for 24 hr. Post-incubation with 5 micro-M of piperine or 100 micro-M of trolox reversed LPS-induced glutathione diminution but did not alter LPS-induced nitrite accumulation in cultured glial cells. These results suggest that piperine, especially at low concentrations, might have stimulatory effect on glial cell metabolic activity and facilitate glial cell functions in brain inflammatory responses.