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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #205737
Title: Inhibitory effects of Blueberry Extract on the Production of Inflammatory Mediators in LPS-activated BV2 Microglia

Author
item Lau, Francis
item BIELINSKI, DONNA - TUFTS UNIVERSITY
item Joseph, James

Submitted to: Journal of Neuroscience Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/26/2006
Publication Date: 1/30/2007
Citation: Lau, F.C., Bielinski, D., Joseph, J.A. 2007. Inhibitory effects of Blueberry Extract on the Production of Inflammatory Mediators in LPS-activated BV2 Microglia. Journal of Neuroscience Research. 85:1010-1017.

Interpretive Summary: Microglial cells are important support cells located in the brain and spinal cord that clean up debris left by other cells. Nonadaptive, overactive microglial activation in the brain and spinal cord has been extensively investigated in age-related brain degenerative diseases and has postulated to lead to brain cell loss. Recent studies have shown that anti-inflammatory drugs may suppress microglial activation and thus, protect against their overactivation and subsequent cell loss. Research also suggest that fruits such as berries may contain both antioxidant and anti-inflammatory compounds that may be important in this regard. Our previous research showed the blueberry extract was effective in preventing deficits in certain cells. Extrapolating from these findings, the current study investigated the effect of blueberry extract on preventing inflammation-induced activation of microglia. Results indicated that treatment with blueberry extract significantly inhibited both the production of inflammation and cytokines, the result of inflammation which cycles causing more inflammation. Also, RNA and protein levels of COX-2, which also is a result of and causes inflammation, were significantly reduced by treatments with blueberry extract. The results suggest that blueberries attenuate inflammatory responses of brain microglia and could be potentially useful in controlling inflammatory conditions in the brain and spinal cord.

Technical Abstract: Sustained microglial activation in the central nervous system (CNS) has been extensively investigated in age-related neurodegenerative diseases and has been postulated to lead to neuronal cell loss in these conditions. Recent studies have shown that anti-inflammatory drugs may suppress microglial activation and thus, protect against microglial overactivation and subsequent cell loss. Research also suggests that fruits such as berries may contain both antioxidant and anti-inflammatory polyphenols that may be important in this regard. Our previous research showed that blueberry extract was effective in preventing oxidant-induced calcium response deficits in M1 (muscarinic receptor)-transfected COS-7 cells. Extrapolating from these findings, the current study investigated the effect of blueberry extract on preventing inflammation induced activation of microglia. BV2 murine microglial cells were stimulated with the bacterial endotoxin, lipopolysaccharide (LPS), followed by treatments with varying concentrations of blueberry extract. The production of cytokines in the cell conditioned media (CCM) was analyzed by ELISA (Enzyme-Linked ImmunoSorbent Assay) and the amount of nitric oxide (NO) in CCM was measured with Griess reagent. The cellular levels of mRNA and protein of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were assessed by quantitative real-time RT-PCR and western blot, respectively. Results indicated that treatments with blueberry extract inhibited the production of the inflammatory mediator, nitric oxide (NO), as well as the cytokines, interleukin-1 beta and tumor necrosis factor-alpha, in cell conditioned media from LPS-activated BV2 microglia. Also, mRNA and protein levels of iNOS and COX-2 in LPS-activated BV2 cells were significantly reduced by treatments with blueberry extract. The results suggest that blueberry polyphenols attenuate inflammatory responses of brain microglia and could be potentially useful in modulation of inflammatory conditions in the CNS.