Singh Sandeep, Singh Abhishek Kumar, Garg Geetika, Rizvi Syed Ibrahim
Department of Biochemistry, University of Allahabad, Allahabad 211002, India.
Department of Biochemistry, University of Allahabad, Allahabad 211002, India.
Life Sci. 2018 Jan 15;193:171-179. doi: 10.1016/j.lfs.2017.11.004. Epub 2017 Nov 7.
In the present study, attempts have been made to evaluate the potential role of fisetin, a caloric restriction mimetic (CRM), for neuroprotection in D-galactose (D-gal) induced accelerated and natural aging models of rat.
Fisetin was supplemented (15mg/kg b.w., orally) to young, D-gal induced aged (D-gal 500mg/kg b.w subcutaneously) and naturally aged rats for 6weeks. Standard protocols were employed to measure pro-oxidants, antioxidants and mitochondrial membrane potential in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy, neuronal, aging as well as inflammatory marker genes. We have also evaluated apoptotic cell death and synaptosomal membrane-bound ion transporter activities in brain tissues.
Our data demonstrated that fisetin significantly decreased the level of pro-oxidants and increased the level of antioxidants. Furthermore, fisetin also ameliorated mitochondrial membrane depolarization, apoptotic cell death and impairments in the activities of synaptosomal membrane-bound ion transporters in aging rat brain. RT-PCR data revealed that fisetin up-regulated the expression of autophagy genes (Atg-3 and Beclin-1), sirtuin-1 and neuronal markers (NSE and Ngb), and down-regulated the expression of inflammatory (IL-1β and TNF-α) and Sirt-2 genes respectively in aging brain.
The present study suggests that fisetin supplementation may provide neuroprotection against aging-induced oxidative stress, apoptotic cell death, neuro-inflammation, and neurodegeneration in rat brain.
在本研究中，已尝试评估杨梅素（一种热量限制模拟物，CRM）在D-半乳糖（D-gal）诱导的大鼠加速衰老和自然衰老模型中对神经保护的潜在作用。
对年轻大鼠、D-gal诱导的衰老大鼠（皮下注射D-gal 500mg/kg体重）和自然衰老大鼠补充杨梅素（15mg/kg体重，口服），持续6周。采用标准方案测量脑组织中的促氧化剂、抗氧化剂和线粒体膜电位。进行逆转录聚合酶链反应（RT-PCR）基因表达分析，以评估自噬、神经元、衰老以及炎症标记基因的表达。我们还评估了脑组织中的凋亡细胞死亡和突触体膜结合离子转运体活性。
我们的数据表明，杨梅素显著降低了促氧化剂水平并提高了抗氧化剂水平。此外，杨梅素还改善了衰老大鼠脑中线粒体膜去极化、凋亡细胞死亡以及突触体膜结合离子转运体活性的损伤。RT-PCR数据显示，杨梅素上调了衰老脑中自噬基因（Atg-3和Beclin-1）、沉默调节蛋白1和神经元标记物（NSE和Ngb）的表达，并分别下调了炎症（IL-1β和TNF-α）和Sirt-2基因的表达。
本研究表明，补充杨梅素可能为大鼠脑提供针对衰老诱导的氧化应激、凋亡细胞死亡、神经炎症和神经退行性变的神经保护作用。
