Luteolin Shows an Antidepressant-Like Effect via Suppressing Endoplasmic Reticulum Stress
Luteolin Shows an Antidepressant-Like Effect via Suppressing Endoplasmic Reticulum Stress
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DOI：
10.1248/bpb.34.1481
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发表时间：
2011-09-01
影响因子：
2
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Ishisaka, Mitsue;Kakefuda, Kenichi;Hara, Hideaki
抑郁症是一个重要的公共卫生问题，一些报告表明抑郁症和内质网应激之间的关联。木犀草素是一种黄酮类化合物，存在于许多植物中，具有抗炎、抗焦虑、改善记忆等多种药理学特性，这表明木犀草素可以渗透到大脑中。在本研究中，我们研究了木犀草素对内质网应激诱导的神经细胞死亡的影响。在人神经母细胞瘤细胞中，1至10克的木犀草素显著抑制衣霉素诱导的细胞死亡。木犀草素增加了78 kDa葡萄糖调节蛋白和94 kDa葡萄糖调节蛋白的表达，并降低了caspase-3的切割活化。此外，为了研究长期木樨草素治疗是否具有抗抑郁作用，我们进行了一些行为测试。长期木樨草素治疗在行为测试中显示出抗抑郁样作用，并且木樨草素减弱皮质酮治疗抑郁模型小鼠海马中内质网应激相关蛋白的表达。这些发现表明，毛地黄黄酮具有抗抑郁样作用，部分是由于抑制内质网应激。
Depression is a significant public health problem and some reports indicate an association between depression and endoplasmic reticulum stress. Luteolin is a flavonoid contained in many plants and with a variety of known pharmacological properties such as anti-inflammatory, anti-anxiety, and memory-improving effects, suggesting that luteolin penetrates into the brain. In the present study, we investigated the effects of luteolin on endoplasmic reticulum stress-induced neuronal cell death. Luteolin significantly suppressed tunicamycin-induced cell death at 1 to 10 gm in human neuroblastoma cells. Luteolin increased in the expression of the 78 kDa glucose-regulated protein and 94 kDa glucose-regulated protein and decreased in the cleavage activation of caspase-3. Additionally, to investigate whether chronic luteolin treatment has an antidepression effect, we performed some behavioral tests. Chronic luteolin treatment showed antidepressant-like effects in behavioral tests and, luteolin attenuated the expression of endoplasmic reticulum stress-related proteins in the hippocampus of corticosterone-treated depression model mice. These findings indicate that luteolin has antidepressant-like effects, partly due to the suppression of endoplasmic reticulum stress.