Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress
Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress
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来自Gentiana rigescens Franch 的Amarogentin 通过抗氧化应激表现出抗衰老和神经保护作用
DOI：
10.1155/2020/3184019
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发表时间：
2020-08-03
影响因子：
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通讯作者：
Qi, Jianhua
中科院分区：
文献类型：
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作者：
Disasa, Dejene;Cheng, Lihong;Qi, Jianhua
本研究采用酵母菌复制寿命法指导中药龙胆抗衰老物质的分离。分离得到一种具有抗衰老作用的化合物，通过光谱分析确定其化学结构为紫红色，并与文献报道的数据进行了比较。在1、3和10MU的剂量下显著延长了K6001酵母的复制寿命。此外，还通过提高过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPX)的活性以及这些酶的基因表达来提高酵母在氧化应激下的存活率。此外，该化合物没有延长K6001背景的sod1、sod2、uth1和skn7突变体的复制寿命。这些结果表明，苋菜红素可能通过提高酵母菌SOD2、CAT、GPx基因的表达、酶活性和抗氧化应激而发挥抗衰老作用。此外，我们利用PC12细胞系统对该天然产物的抗氧化活性进行了评估，PC12细胞系统是在细胞水平上研究神经系统的有用模型。Amarogentin显著提高了过氧化氢诱导的PC12细胞的存活率，提高了细胞内超氧化物歧化酶和超氧化物歧化酶的活性，增加了超氧化物歧化酶、过氧化氢酶、GPx、Nrf2和Bcl-x1的基因表达。同时，苦参素能显著降低PC12细胞内的活性氧(ROS)和丙二醛(MDA)水平。这些结果表明，抗氧化应激对苋菜红素的抗衰老和神经保护作用具有重要作用。有趣的是，苋菜红素在PC12细胞中显示出神经再生活性。因此，天然产物中，紫红色来源于G。Rigescens具有抗氧化活性，可能是开发治疗神经退行性疾病药物的良好候选分子。
In the present study, the replicative lifespan assay of yeast was used to guide the isolation of antiaging substance fromGentiana rigescensFranch, a traditional Chinese medicine. A compound with antiaging effect was isolated, and the chemical structure of this molecule as amarogentin was identified by spectral analysis and compared with the reported data. It significantly extended the replicative lifespan of K6001 yeast at doses of 1, 3, and 10 mu M. Furthermore, amarogentin improved the survival rate of yeast under oxidative stress by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and these enzymes' gene expression. In addition, this compound did not extend the replicative lifespan ofsod1,sod2,uth1, andskn7mutants with K6001 background. These results suggested that amarogentin exhibited antiaging effect on yeast via increase ofSOD2,CAT,GPxgene expression, enzyme activity, and antioxidative stress. Moreover, we evaluated antioxidant activity of this natural products using PC12 cell system, a useful model for studying the nervous system at the cellular level. Amarogentin significantly improved the survival rate of PC12 cells under H2O2-induced oxidative stress and increased the activities of SOD and SOD2, and gene expression ofSOD2,CAT,GPx,Nrf2, andBcl-x1. Meanwhile, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) of PC12 cells were significantly reduced after treatment of the amarogentin. These results indicated that antioxidative stress play an important role for antiaging and neuroprotection of amarogentin. Interestingly, amarogentin exhibited neuritogenic activity in PC12 cells. Therefore, the natural products, amarogentin fromG. rigescenswith antioxidant activity could be a good candidate molecule to develop drug for treating neurodegenerative diseases.