College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035, China.
Chem Biol Interact. 2012 Sep 30;199(3):137-42. doi: 10.1016/j.cbi.2012.07.001. Epub 2012 Jul 20.
Oxidative stress plays an important role in the progression of many chronic diseases including cardiovascular diseases, diabetes, cancer and neurodegenerative disorders. One such mediator of oxidative stress is peroxynitrite, which is highly toxic to cultured neurons and astrocytes, and has been reported to be involved in the pathogenesis of various types of neuronal diseases. Therefore, searching for natural compounds with peroxynitrite-scavenging activity might be an effective therapy for peroxynitrite-mediated cytotoxicity. Hispidin, a phenolic compound from Phellinus linteus (a medicinal mushroom), has been shown to possess strong antioxidant, anticancer, and antidiabetic properties. However, the astrocyte protective efficacy of hispidin has been not examined. This study was undertaken to investigate whether the astrocyte protective effect of hispidin is associated with inhibition of peroxynitrite-induced DNA damage, a critical event leading to peroxynitrite-mediated cytotoxicity. Our results showed that peroxynitrite can cause DNA damage in φX-174 plasmid DNA and rat primary astrocytes. The presence of hispidin (10-20 μg/ml) was found to significantly inhibit peroxynitrite-induced DNA damage and cytotoxicity. EPR spectroscopy demonstrated that the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from peroxynitrite, and that hispidin potently diminished the adduct signal in a concentration-dependent manner. Taken together, these results demonstrate for the first time that hispidin can protect against peroxynitrite-mediated cytotoxicity, DNA damage and hydroxyl radical formation.
氧化应激在许多慢性疾病的进展中起着重要作用，包括心血管疾病、糖尿病、癌症和神经退行性疾病。过氧亚硝酸盐是氧化应激的一种介质，对培养的神经元和星形胶质细胞具有高度毒性，并已被报道参与各种类型的神经元疾病的发病机制。因此，寻找具有过氧亚硝酸盐清除活性的天然化合物可能是治疗过氧亚硝酸盐介导的细胞毒性的有效方法。从药用蘑菇灵芝（Phellinus linteus）中分离得到的酚类化合物灵芝素已被证明具有很强的抗氧化、抗癌和抗糖尿病特性。然而，灵芝素对星形胶质细胞的保护作用尚未得到检验。本研究旨在探讨灵芝素对星形胶质细胞的保护作用是否与抑制过氧亚硝酸盐诱导的 DNA 损伤有关，而过氧亚硝酸盐诱导的 DNA 损伤是导致过氧亚硝酸盐介导的细胞毒性的关键事件。我们的研究结果表明，过氧亚硝酸盐可引起 φX-174 质粒 DNA 和大鼠原代星形胶质细胞的 DNA 损伤。发现灵芝素（10-20 μg/ml）可显著抑制过氧亚硝酸盐诱导的 DNA 损伤和细胞毒性。电子顺磁共振波谱（EPR）表明，过氧亚硝酸盐形成 DMPO-羟基自由基加合物（DMPO-OH），并且灵芝素以浓度依赖的方式强烈减弱加合物信号。综上所述，这些结果首次表明灵芝素可以防止过氧亚硝酸盐介导的细胞毒性、DNA 损伤和羟基自由基形成。
