Okuyama Satoshi, Morita Mayu, Kaji Miki, Amakura Yoshiaki, Yoshimura Morio, Shimamoto Koji, Ookido Yu, Nakajima Mitsunari, Furukawa Yoshiko
Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan.
Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan.
Molecules. 2015 Nov 10;20(11):20230-9. doi: 10.3390/molecules201119691.
The anti-inflammatory activity of auraptene (AUR), a citrus coumarin, in peripheral tissues is well-known, and we previously demonstrated that AUR exerts anti-inflammatory effects in the ischemic brain; the treatment of mice with AUR for eight days immediately after ischemic surgery suppressed demise and neuronal cell death in the hippocampus, possibly through its anti-inflammatory effects in the brain. We suggested that these effects were at least partly mediated by the suppression of inflammatory mediators derived from astrocytes. The present study showed that (1) AUR, as a pretreatment for five days before and another three days after ischemic surgery, suppressed microglial activation, cyclooxygenase (COX)-2 expression in astrocytes, and COX-2 mRNA expression in the hippocampus; (2) AUR suppressed the lipopolysaccharide-induced expression of COX-2 mRNA and the mRNA of pro-inflammatory cytokines in cultured astrocytes; (3) AUR was still detectable in the brain 60 min after its intraperitoneal administration. These results support our previous suggestion that AUR directly exerts anti-inflammatory effects on the brain.
柑橘类香豆素奥瑞烯醇(AUR)在外周组织中的抗炎活性是众所周知的,并且我们之前证明AUR在缺血性脑中发挥抗炎作用;缺血手术后立即用AUR对小鼠进行为期八天的治疗可抑制海马体中的细胞死亡和神经元细胞死亡,这可能是通过其在脑中的抗炎作用实现的。我们认为这些作用至少部分是由对源自星形胶质细胞的炎症介质的抑制介导的。本研究表明:(1)作为缺血手术前五天和手术后另外三天的预处理,AUR可抑制小胶质细胞活化、星形胶质细胞中环氧合酶(COX)-2的表达以及海马体中COX-2 mRNA的表达;(2)AUR可抑制脂多糖诱导的培养星形胶质细胞中COX-2 mRNA和促炎细胞因子mRNA的表达;(3)腹腔注射AUR 60分钟后仍可在脑中检测到AUR。这些结果支持了我们之前的观点,即AUR直接对脑发挥抗炎作用。