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Int. J. Mol. Sci. 2013, 14(3), 4461-4475; doi:10.3390/ijms14034461

A Steroidal Saponin from Ophiopogon japonicus Extends the Lifespan of Yeast via the Pathway Involved in SOD and UTH1

1,*  and 1
1 College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China 2 College of Biology and Science, Sichuan Agricultural University, Yaan, Sichuan 625014, China 3 Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Chiba 263-8522, Japan
* Author to whom correspondence should be addressed.
Received: 14 January 2013 / Revised: 16 February 2013 / Accepted: 18 February 2013 / Published: 25 February 2013
(This article belongs to the Special Issue Oxidative Stress and Ageing)
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Nolinospiroside F is a steroidal saponin isolated from Ophiopogon japonicus (O. japonicus). In this study, we found that nolinospiroside F significantly extends the replicative lifespan of K6001 yeast at doses of 1, 3 and 10 μM, indicating that it has an anti-aging effect. This may be attributed to its anti-oxidative effect, as nolinospiroside F could increase yeast survival under oxidative stress conditions and decrease the level of malondialdehyde (MDA), an oxidative stress biomarker. It could also increase anti-oxidative stress genes, SOD1 and SOD2, expression, and the activity of superoxide dismutase (SOD). It increase the activity of SIRT1, an upstream inducer of SOD2 expression. In sod1 and sod2 mutant yeast strains, nolinospiroside F failed to extend their replicative lifespan. These results indicate that SOD participates in the anti-aging effect of nolinospiroside F. Furthermore, nolinospiroside F inhibited the expression of UTH1, a yeast-aging gene that is involved in the oxidative stress of yeast, and failed to extend the replicative lifespan of uth1 or skn7 mutant yeast cells. SKN7 is the transcriptional activator of UTH1. We also demonstrate that SOD and UTH1 regulate each other’s expression. Together, these results suggest that SOD and UTH1 genes are required for and play interactive roles in nolinospiroside F-mediated yeast lifespan extension.
Keywords: nolinospiroside F; SOD; UTH1; anti-aging; anti-oxidative stress nolinospiroside F; SOD; UTH1; anti-aging; anti-oxidative stress
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sun, K.; Cao, S.; Pei, L.; Matsuura, A.; Xiang, L.; Qi, J. A Steroidal Saponin from Ophiopogon japonicus Extends the Lifespan of Yeast via the Pathway Involved in SOD and UTH1. Int. J. Mol. Sci. 2013, 14, 4461-4475.

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