Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Brain Res Bull. 2021 Jul;172:190-202. doi: 10.1016/j.brainresbull.2021.04.012. Epub 2021 Apr 21.
Neuroinflammation-mediated microglial reactivity is a major process, which explains the increased risk of Alzheimer's disease (AD) development in patients with Type 2 diabetes mellitus (T2DM). Advanced glycation end products (AGEs), formed by hyperglycemic condition in diabetes, is characterized as an intermediary of brain injury with diabetes through induction of microglial reactivity. Here, we explored the effect of AGEs on microglial reactivity using BV2 as a model. The NF-κB, p38 and JNK pathways were found to be important mechanism in AGEs-induced BV2 microglial reactivity. NF-κB inhibitor (BAY-11-7082), p38 inhibitor (SB203580) and JNK inhibitor (SP600125) exhibited the potential inhibition of AGEs-induced NO production. We also found that the sesamin, a major lignan found in sesame seed oils, exerts an anti-inflammatory effect under AGEs-induced microglial reactivity via suppressing the phosphorylation of NF-κB, p38 and JNK pathways. Moreover, sesamin also ameliorated AGEs-induced-receptor for advanced glycation end products (RAGE) expression. Taken together, sesamin may be a promising phytochemical compound to delay inflammatory progress by AGEs microglia function. Similarly, inhibition of AGEs-induced microglial reactivity might be potential therapeutic targets of neuroinflammation-based mechanisms in T2DM link progressive AD.
神经炎症介导的小胶质细胞反应是一个主要过程，它解释了 2 型糖尿病（T2DM）患者阿尔茨海默病（AD）发展风险增加的原因。在糖尿病中，由高血糖形成的晚期糖基化终产物（AGEs）被认为是通过诱导小胶质细胞反应导致糖尿病脑损伤的中介物。在这里，我们使用 BV2 作为模型来研究 AGEs 对小胶质细胞反应的影响。发现 NF-κB、p38 和 JNK 通路是 AGEs 诱导的 BV2 小胶质细胞反应的重要机制。NF-κB 抑制剂（BAY-11-7082）、p38 抑制剂（SB203580）和 JNK 抑制剂（SP600125）表现出抑制 AGEs 诱导的 NO 产生的潜力。我们还发现，芝麻素，一种在芝麻油中发现的主要木脂素，通过抑制 NF-κB、p38 和 JNK 通路的磷酸化，在 AGEs 诱导的小胶质细胞反应中发挥抗炎作用。此外，芝麻素还改善了 AGEs 诱导的晚期糖基化终产物（RAGE）受体的表达。总之，芝麻素可能是一种有前途的植物化学化合物，可以通过抑制 AGEs 诱导的小胶质细胞功能来延缓炎症进展。同样，抑制 AGEs 诱导的小胶质细胞反应可能是 T2DM 中与神经炎症相关的机制与进行性 AD 相关的潜在治疗靶点。
