Roles of 4′-O-Methylalpinum Isoflavone on Activation of Microglia Induced by Oxysterols

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'-<i>O</i>-Methylalpinum isoflavone (mAI), derived from <i>Cudrania tricuspidata</i> 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.