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In the present study, the replicative lifespan assay of yeast was used to guide the isolation of antiaging substance from  Gentiana rigescens  Franch, 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  μ 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 of  sod1 ,  sod2 ,  uth1 , and  skn7  mutants with K6001 background. These results suggested that amarogentin exhibited antiaging effect on yeast via increase of  SOD2 ,  CAT ,  GPx  gene 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 H 2 O 2 -induced oxidative stress and increased the activities of SOD and SOD2, and gene expression of  SOD2 ,  CAT ,  GPx ,  Nrf2 , and  Bcl-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 from  G. rigescens  with antioxidant activity could be a good candidate molecule to develop drug for treating neurodegenerative diseases.

Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress