Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids (apigenin and luteolin) on the production of IL-31 and IL-33 in lipopolysaccharide (LPS)-activated astrocytes. Cell viability was investigated using EZ-Cytox assay, mRNA expressions of IL-31 and IL-33 were analyzed by RT-PCR, protein expressions were analyzed by western blot, and cytokine secretion was analyzed by ELISA. Apigenin and luteolin prevented astrocyte activation and inhibited mRNA and protein expression and secretion of IL-31 and IL-33 in the LPS-treated astrocytes. Apigenin’s suppression of ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 and IL-33, while luteolin’s suppression of JNK, p38, ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 in the astrocytes. Also, luteolin’s suppression of ERK, NF-κB, and STAT3 activations inhibited IL-33 production in the activated astrocytes. In addition, apigenin and luteolin also prevented the translocation of activated STAT3 and NF-κB to the nucleus of the activated astrocytes and subsequently affected their DNA binding activities. The results suggest that apigenin and luteolin may have potentials as neuroprotective agents for the treatment of diseases involving astrocyte activation and detrimental production of IL-31 and IL-33.

星形胶质细胞释放生物活性物质，引起神经退行性疾病的炎症。本研究调查了两种类黄酮（芹菜素和木犀草素）对脂多糖（LPS）激活的星形胶质细胞中IL-31和IL-33产生的影响。用EZ-Cytox法检测细胞活力，通过RT-PCR分析IL-31和IL-33的mRNA表达，通过蛋白质印迹分析蛋白质的表达，通过ELISA分析细胞因子的分泌。芹菜素和木犀草素可防止星形胶质细胞活化，并抑制LPS处理的星形胶质细胞中mRNA和蛋白质的表达以及IL-31和IL-33的分泌。芹菜素对ERK，NF-κB和STAT3激活的抑制作用是抑制IL-31和IL-33的原因，而木犀草素对JNK，p38，ERK，NF-κB的抑制作用是，STAT3激活是星形胶质细胞中IL-31抑制的原因。此外，木犀草素对ERK，NF-κB和STAT3激活的抑制作用抑制了激活的星形胶质细胞中IL-33的产生。此外，芹菜素和木犀草素还阻止活化的STAT3和NF-κB向活化的星形胶质细胞核易位，进而影响其DNA结合活性。结果表明，芹菜素和木犀草素可能具有潜在的神经保护作用，可用于治疗涉及星形胶质细胞活化和IL-31和IL-33有害产生的疾病。芹菜素和木犀草素还阻止活化的STAT3和NF-κB向活化的星形胶质细胞核易位，进而影响其DNA结合活性。结果表明，芹菜素和木犀草素可能具有潜在的神经保护作用，可用于治疗涉及星形胶质细胞活化和IL-31和IL-33有害产生的疾病。芹菜素和木犀草素还阻止活化的STAT3和NF-κB向活化的星形胶质细胞核易位，进而影响其DNA结合活性。结果表明，芹菜素和木犀草素可能具有潜在的神经保护作用，可用于治疗涉及星形胶质细胞活化和IL-31和IL-33有害产生的疾病。