Sun Yujuan, Lin Yanfei, Cao Xueli, Xiang Lan, Qi Jianhua
College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China.
Int J Mol Sci. 2014 Nov 25;15(12):21660-73. doi: 10.3390/ijms151221660.
For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS) assays, and malondialdehyde (MDA) tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF) mimic activities again confirmed their neuroprotective function.
为了从海洋天然产物中筛选抗衰老样品，采用K6001酵母菌株作为生物测定系统。将活性贻贝提取物进行分离，得到一个活性甾醇组分（SF）。对SF进一步纯化，获得了四种甾醇化合物。确定它们的结构分别为胆固醇（CHOL）、油菜甾醇、环甾醇和24-亚甲基胆固醇。所有化合物均表现出相似的抗衰老活性。为了解其中涉及的作用机制，对含量最丰富的化合物CHOL进行了抗氧化实验、活性氧（ROS）测定和丙二醛（MDA）测试。结果表明，用CHOL处理可提高酵母在氧化应激下的存活率，并降低ROS和MDA水平。此外，利用具有K6001背景的uth1、skn7、sod1和sod2突变体，且这些突变体的寿命不受CHOL影响。这些结果表明，CHOL通过抗氧化应激发挥抗衰老作用。基于神经保护与抗衰老之间的联系，在PC12细胞中进行了神经保护实验。用百草枯诱导氧化应激，结果表明CHOL和SF可保护PC12细胞免受百草枯诱导的损伤。此外，这些物质表现出神经生长因子（NGF）模拟活性，再次证实了它们的神经保护功能。
