Department of Drug Sciences, Section of Biochemistry, University of Catania, Catania, Italy.
Neurosci Lett. 2011 Oct 31;504(3):252-6. doi: 10.1016/j.neulet.2011.09.041. Epub 2011 Sep 28.
Diabetes mellitus is associated with a higher oxidative stress and reduced activity of the antioxidant defense system in different brain regions. Results from numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents. It is well established that polyphenols exert potent antioxidant and protective functions. Based on recent findings, one potential target for the antioxidant/antinflammatory properties of polyphenols is the heme oxygenase (HO)-1 pathway. Among various compounds tested silibinin, the main component of silymarin, has been shown to possess a strong antioxidant effect in various experimental models; however a study on the possible neuroprotective effect of this compound on the brain of diabetic animals is currently lacking. Therefore, we studied and measured in lean mice (db/m) and knock out mice for the leptin receptors mice (db/db) the effect of silibinin on HO-1 protein levels, non proteic thiol groups, isoprostanes and 8-OH deoxyguanosine (markers of lipid peroxidation and DNA damage, respectively) in different brain regions. Our results showed that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition.
糖尿病与不同脑区氧化应激增加和抗氧化防御系统活性降低有关。许多研究的结果表明，糖尿病患者的认知和神经化学功能受损，链脲佐菌素诱导的糖尿病啮齿动物也是如此。多酚具有很强的抗氧化和保护作用，这一点已得到充分证实。基于最近的发现，多酚的抗氧化/抗炎特性的一个潜在靶点是血红素加氧酶 (HO)-1 途径。在各种测试的化合物中，水飞蓟素（水飞蓟宾的主要成分）已被证明在各种实验模型中具有很强的抗氧化作用；然而，目前缺乏关于这种化合物对糖尿病动物大脑可能具有的神经保护作用的研究。因此，我们在瘦鼠 (db/m) 和瘦素受体敲除小鼠 (db/db) 中研究和测量了水飞蓟素对不同脑区 HO-1 蛋白水平、非蛋白巯基、异前列腺素和 8-OH 脱氧鸟苷（分别为脂质过氧化和 DNA 损伤的标志物）的影响。我们的结果表明，与瘦鼠相比，db/db 小鼠的不同脑区 HO-1 表达不同。此外，水飞蓟素通过激活 HO 系统提供 DNA 保护并减少特定脑区的氧化应激。水飞蓟素可能为对抗糖尿病状态下中枢神经系统中的氧化应激提供一种有效的工具。
