Abstract
BackgroundSecoisolariciresinol diglucoside (SDG), the main lignan in flaxseed, is known for its beneficial effects in inflammation, oxidative stress, heart disease, tumor progression, atherosclerosis, and diabetes. SDG might be an attractive natural compound that protects against neuroinflammation. Yet, there are no comprehensive studies to date investigating the effects of SDG on brain endothelium using relevant in vivo and in vitro models.MethodsWe evaluated the effects of orally administered SDG on neuroinflammatory responses using in vivo imaging of the brain microvasculature during systemic inflammation and aseptic encephalitis. In parallel, the anti-inflammatory actions of SDG on brain endothelium and monocytes were evaluated in vitro blood-brain barrier (BBB) model. Multiple group comparisons were performed by one-way analysis of variance with Dunnet’s post hoc tests.ResultsWe found that SDG diminished leukocyte adhesion to and migration across the BBB in vivo in the setting of aseptic encephalitis (intracerebral TNFα injection) and prevented enhanced BBB permeability during systemic inflammatory response (LPS injection). In vitro SDG pretreatment of primary human brain microvascular endothelial cells (BMVEC) or human monocytes diminished adhesion and migration of monocytes across brain endothelial monolayers in conditions mimicking CNS inflammatory responses. Consistent with our in vivo observations, SDG decreased expression of the adhesion molecule, VCAM1, induced by TNFα, or IL-1β in BMVEC. SDG diminished expression of the active form of VLA-4 integrin (promoting leukocyte adhesion and migration) and prevented the cytoskeleton changes in primary human monocytes activated by relevant inflammatory stimuli.ConclusionThis study indicates that SDG directly inhibits BBB interactions with inflammatory cells and reduces the inflammatory state of leukocytes. Though more work is needed to determine the mechanism by which SDG mediates these effects, the ability of SDG to exert a multi-functional response reducing oxidative stress, inflammation, and BBB permeability makes it an exciting potential therapeutic for neuroinflammatory diseases. SDG can serve as an anti-inflammatory and barrier-protective agent in neuroinflammation.
Highlights
Secoisolariciresinol diglucoside (SDG), the main lignan in flaxseed, is known for its beneficial effects in inflammation, oxidative stress, heart disease, tumor progression, atherosclerosis, and diabetes
SDG administration diminishes leukocyte adhesion and migration across blood-brain barrier (BBB) in neuroinflammation It was documented before that SDG administration in vivo diminished end-organ injury in models of systemic inflammation and lung radiation injury
This study indicates that SDG directly inhibits BBB interactions with inflammatory cells while reducing the inflammatory state of leukocytes
Summary
Secoisolariciresinol diglucoside (SDG), the main lignan in flaxseed, is known for its beneficial effects in inflammation, oxidative stress, heart disease, tumor progression, atherosclerosis, and diabetes. Secoisolariciresinol diglucoside (SDG), is the main lignan in wholegrain flaxseed, known for its beneficial effects including anti-inflammatory, antioxidant, antimutagenic, anti-microbial, anti-obesity, hypolipidemic, and neuroprotective effects. SDG has been shown to be effective in several preclinical models of diseases in which oxidative stress and inflammation play a prominent role in pathogenesis, including heart disease [2,3,4] and diabetes [5, 6]. SDG showed positive effects in cancer [4, 7, 8], liver [9, 10], and kidney inflammation as well as in obesity and the metabolic syndrome [10, 11]. SDG can attenuate respiratory bursts in activated lung macrophages [19] suggesting anti-inflammatory roles for SDG in this cell population
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