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A Steroidal Saponin from Ophiopogon japonicus Extends the Lifespan of Yeast via the Pathway Involved in SOD and UTH1
College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China
College of Biology and Science, Sichuan Agricultural University, Yaan, Sichuan 625014, China
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; in revised form: 16 February 2013 / Accepted: 18 February 2013 / Published: 25 February 2013
Abstract: 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
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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.
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. International Journal of Molecular Sciences. 2013; 14(3):4461-4475.
Sun, Kaiyue; Cao, Shining; Pei, Liang; Matsuura, Akira; Xiang, Lan; Qi, Jianhua. 2013. "A Steroidal Saponin from Ophiopogon japonicus Extends the Lifespan of Yeast via the Pathway Involved in SOD and UTH1." Int. J. Mol. Sci. 14, no. 3: 4461-4475.