Secoisolariciresinol diglucoside is a blood-brain barrier protective and anti-inflammatory agent: implications for neuroinflammation

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.

The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial

“…This finding was consistent with those of the previous studies [42,43]. Secoisolariciresinol Diglucoside (SDG) is an active compound in flaxseed, which has anti-inflammatory effects [44]. Flaxseed also contains a high amount of soluble fiber fermented to short-chain fatty acids (acetate, propionate, and butyrate) by intestinal bacteria.…”

Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction

“…www.nature.com/scientificreports www.nature.com/scientificreports/ of occludin oligomeric assemblies in animals subjected to hypoxia and reoxygenation 41 . Here, we investigated the effects of another molecule; secoisolariciresinol diglucoside (SDG), a major lignan found in flaxseeds that has been hypothesized to have beneficial effects against diabetes, tumor progression, atherosclerosis, heart disease, oxidative stress, and inflammation 42 . SDG has also been shown to have BBB protective effects and anti-inflammatory properties due to its direct free radical scavenging activity [43][44][45] .…”

Specific Dietary (Poly)phenols Are Associated with Sleep Quality in a Cohort of Italian Adults

“…Several studies have shown that molecules of interest from our study, including some flavonoids (i.e., apigenin) and hydroxycinnamic acids, improve cell antioxidant activity against oxidative stress in the central nervous system [64,65]. Additionally, lignans have been demonstrated to exert anti-oxidative and anti-inflammatory properties in neurons and protect the blood-brain barrier against inflammatory cells by reducing oxidative stress, inflammation and permeability [66][67][68]. Dietary (poly)phenols may ameliorate poor endothelial function [69] and help to control blood pressure [70], which, in turn, has been associated with measures of sleep quality together with decreases in the percentage of REM sleep and increases in REM sleep latency [71][72][73].…”