Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Mysore, India.
Neurotoxicology. 2013 Jan;34:150-9. doi: 10.1016/j.neuro.2012.11.002. Epub 2012 Nov 19.
Nitrosylation of tyrosine (3-nitro tyrosine, 3-NT) has been implicated in the pathophysiology of various disorders particularly neurodegenerative conditions and aging. Cyperus rotundus rhizome is being used as a traditional folk medicine to alleviate a variety of disorders including neuronal stress. The herb has recently found applications in food and confectionary industries also. In current study, we have explored the protective effects of C. rotundus rhizome extract (CRE) through its oxido-nitrosative and anti apoptotic mechanism to attenuate peroxynitrite (ONOO(-)) induced neurotoxicity using human neuroblastoma SH-SY5Y cells. Our results elucidate that pre-treatment of neurons with CRE ameliorates the mitochondrial and plasma membrane damage induced by 500 μM SIN-1 to 80% and 24% as evidenced by MTT and LDH assays. CRE inhibited NO generation by downregulating i-NOS expression. SIN-1 induced depletion of antioxidant enzyme status was also replenished by CRE which was confirmed by immunoblot analysis of SOD and CAT. The CRE pre-treatment efficiently potentiated the SIN-1 induced apoptotic biomarkers such as bcl-2 and caspase-3 which orchestrate the proteolytic damage of the cell. The ONOO(-) induced damage to cellular, nuclear and mitochondrial integrity was also restored by CRE. Furthermore, CRE pre-treatment also regulated the 3-NT formation which shows the potential of plant extract against tyrosine nitration. Taken together, our findings suggest that CRE might be developed as a preventive agent against ONOO(-) induced apoptosis.
酪氨酸的亚硝化作用(3-硝基酪氨酸,3-NT)与多种疾病的病理生理学有关,特别是神经退行性疾病和衰老。香附根茎被用作传统民间药物来缓解各种疾病,包括神经元应激。这种草药最近在食品和糖果行业也得到了应用。在目前的研究中,我们通过其氧化亚硝化和抗细胞凋亡机制,探讨了香附根茎提取物(CRE)的保护作用,以减轻过氧亚硝酸盐(ONOO(-))诱导的人神经母细胞瘤 SH-SY5Y 细胞毒性。我们的结果表明,神经元用 CRE 预处理可改善 500μM SIN-1 引起的线粒体和质膜损伤,MTT 和 LDH 测定表明分别改善了 80%和 24%。CRE 通过下调 iNOS 表达抑制 NO 的产生。CRE 还补充了 SIN-1 诱导的抗氧化酶状态的消耗,这通过 SOD 和 CAT 的免疫印迹分析得到了证实。CRE 预处理有效地增强了 SIN-1 诱导的凋亡生物标志物,如 bcl-2 和 caspase-3,这些生物标志物协调了细胞的蛋白水解损伤。CRE 还恢复了 ONOO(-)诱导的细胞、核和线粒体完整性的损伤。此外,CRE 预处理还调节了 3-NT 的形成,这表明植物提取物具有防止酪氨酸硝化的潜力。综上所述,我们的研究结果表明,CRE 可能被开发为预防 ONOO(-)诱导细胞凋亡的药物。