Son Yonghae, Kim Miran, Lee Dongho, Kwon Ryuk Jun, Kim Koanhoi
Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of Korea.
Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Int J Mol Sci. 2024 Nov 27;25(23):12743. doi: 10.3390/ijms252312743.
Microglia play a crucial role as immune cells responsible for the brain's defense mechanisms. Similar to the actions of macrophages in the body, microglial cells elicit an inflammatory immune response in the brain. Recent papers highlight activated microglial cells as pivotal contributors to inflammatory responses in the brain, leading to damage to nerve tissue and the onset of Alzheimer's disease (AD). In the brains of AD patients, elevated levels of inflammatory cytokines such as interleukin-6 (IL-6) and oxidized cholesterol metabolites (oxysterols) are observed. These factors are closely associated with inflammatory diseases in the brain. 4'--Methylalpinum isoflavone (mAI), derived from fruit, possesses antioxidant, neuroprotective, and anti-inflammatory properties. Consequently, this study examined the effect of mAI on the expression of IL-6, a major inflammatory cytokine. The HMC3 microglial cell line was treated with oxysterols to assess the effectiveness of mAI in mitigating this inflammatory response. The results indicated that mAI inhibited the gene expression and protein secretion of IL-6 induced by 25-hydroxycholesterol (25OHChol) and 27-hydroxycholesterol (27OHChol). Furthermore, the expression of MHC class II, a marker for microglial activation, was reduced to baseline levels. These findings suggest that mAI may serve as a viable option for suppressing and treating brain inflammatory diseases induced by cholesterol oxidation products. This is achieved by curtailing the expression of the inflammatory cytokine resulting from the activation of microglial cells by immuno-oxysterol.
小胶质细胞作为负责大脑防御机制的免疫细胞发挥着关键作用。与体内巨噬细胞的作用类似，小胶质细胞会在大脑中引发炎症免疫反应。最近的论文强调活化的小胶质细胞是大脑炎症反应的关键促成因素，会导致神经组织损伤和阿尔茨海默病（AD）的发病。在AD患者的大脑中，观察到炎症细胞因子如白细胞介素-6（IL-6）和氧化胆固醇代谢物（氧化甾醇）水平升高。这些因素与大脑中的炎症性疾病密切相关。源自果实的4'-甲基高山黄芩素（mAI）具有抗氧化、神经保护和抗炎特性。因此，本研究考察了mAI对主要炎症细胞因子IL-6表达的影响。用氧化甾醇处理HMC3小胶质细胞系，以评估mAI减轻这种炎症反应的有效性。结果表明，mAI抑制了25-羟基胆固醇（25OHChol）和27-羟基胆固醇（27OHChol）诱导的IL-6的基因表达和蛋白分泌。此外，小胶质细胞活化标志物MHC II类分子的表达降低至基线水平。这些发现表明，mAI可能是抑制和治疗由胆固醇氧化产物诱导的脑部炎症性疾病的一个可行选择。这是通过减少免疫氧化甾醇激活小胶质细胞所产生的炎症细胞因子的表达来实现的。
