Nutraceutical agents with anti-inflammatory properties prevent dietary saturated-fat induced disturbances in blood–brain barrier function in wild-type mice

Journal of Neuroinflammation

John C Mamo¹  Corey Giles²  Virginie Lam²  Menuka M Pallebage-Gamarallage²  Ryusuke Takechi¹ 

[1] Centre for Metabolic Fitness, Australian Technology Network, GPO Box U1987, Perth, WA, 6845, Australia;School of Public Health, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Kent st, Bentley, WA, 6102, Australia

关键词: Saturated fatty acids;    Oxidative stress;    Nicotinamide;    Niacin;    Neurodegenerative disorders;    Inflammation;    Blood–brain barrier;    Alpha-lipoic acid;    Garlic extract-aged;   

Others  :  1159949
DOI  :  10.1186/1742-2094-10-73

 received in 2012-12-21, accepted in 2013-06-08,  发布年份 2013

【 摘 要 】

Background

Emerging evidence suggests that disturbances in the blood–brain barrier (BBB) may be pivotal to the pathogenesis and pathology of vascular-based neurodegenerative disorders. Studies suggest that heightened systemic and central inflammations are associated with BBB dysfunction. This study investigated the effect of the anti-inflammatory nutraceuticals garlic extract-aged (GEA), alpha lipoic acid (ALA), niacin, and nicotinamide (NA) in a murine dietary-induced model of BBB dysfunction.

Methods

C57BL/6 mice were fed a diet enriched in saturated fatty acids (SFA, 40% fat of total energy) for nine months to induce systemic inflammation and BBB disturbances. Nutraceutical treatment groups included the provision of either GEA, ALA, niacin or NA in the positive control SFA-group and in low-fat fed controls. Brain parenchymal extravasation of plasma derived immunoglobulin G (IgG) and large macromolecules (apolipoprotein (apo) B lipoproteins) measured by quantitative immunofluorescent microscopy, were used as markers of disturbed BBB integrity. Parenchymal glial fibrillar acidic protein (GFAP) and cyclooxygenase-2 (COX-2) were considered in the context of surrogate markers of neurovascular inflammation and oxidative stress. Total anti-oxidant status and glutathione reductase activity were determined in plasma.

Results

Brain parenchymal abundance of IgG and apoB lipoproteins was markedly exaggerated in mice maintained on the SFA diet concomitant with significantly increased GFAP and COX-2, and reduced systemic anti-oxidative status. The nutraceutical GEA, ALA, niacin, and NA completely prevented the SFA-induced disturbances of BBB and normalized the measures of neurovascular inflammation and oxidative stress.

Conclusions

The anti-inflammatory nutraceutical agents GEA, ALA, niacin, or NA are potent inhibitors of dietary fat-induced disturbances of BBB induced by systemic inflammations.

【 授权许可】

   
2013 Takechi et al.; licensee BioMed Central Ltd.

【 图 表 】

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