Department of Pathology and Laboratory Medicine, Temple University, Philadelphia, PA, 19140, USA.
Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
J Neuroinflammation. 2018 Jan 27;15(1):25. doi: 10.1186/s12974-018-1065-0.
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 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.
We 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.
We 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.
This 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.
木脂素二葡萄糖苷（SDG）是亚麻籽中的主要木脂素，其具有抗炎、抗氧化应激、心脏病、肿瘤进展、动脉粥样硬化和糖尿病等有益作用。SDG 可能是一种有吸引力的天然化合物，可以预防神经炎症。然而，迄今为止，还没有使用相关的体内和体外模型全面研究 SDG 对大脑内皮的影响。
我们使用体内脑微血管炎症反应的影像学方法，评估了口服 SDG 对全身炎症和无菌性脑炎期间神经炎症反应的影响。同时，我们在体外血脑屏障（BBB）模型中评估了 SDG 对大脑内皮和单核细胞的抗炎作用。采用单因素方差分析进行多组比较，并进行 Dunnett 事后检验。
我们发现，SDG 可减少无菌性脑炎（脑内 TNFα 注射）和全身炎症反应（LPS 注射）时 BBB 中白细胞黏附和迁移。体外 SDG 预处理原代人脑微血管内皮细胞（BMVEC）或人单核细胞，可在模拟中枢神经系统炎症反应的条件下减少单核细胞穿过脑内皮单层的黏附和迁移。与我们的体内观察结果一致，SDG 可降低 TNFα 或 IL-1β诱导的 BMVEC 中黏附分子 VCAM1 的表达。SDG 可减少活性形式的 VLA-4 整合素（促进白细胞黏附和迁移）的表达，并防止相关炎症刺激激活的原代人单核细胞的细胞骨架变化。
这项研究表明，SDG 可直接抑制 BBB 与炎症细胞的相互作用，并降低白细胞的炎症状态。尽管需要进一步的工作来确定 SDG 介导这些作用的机制，但 SDG 具有多效性反应的能力，可降低氧化应激、炎症和 BBB 通透性，使其成为神经炎症性疾病的一种令人兴奋的潜在治疗方法。SDG 可作为神经炎症中的抗炎和屏障保护剂。
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