Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction
In the present study, replicative lifespan and chronological lifespan assays of yeast were used to double-screen antiaging compounds from <i>Gentiana rigescens</i> Franch, a Chinese herb medicine. Inokosterone from <i>G. rigescens</i> Franch extended not only the replicative...
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MDPI AG
2022-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/2/214 |
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| author | Yanan Liu Qian Liu Danni Chen Akira Matsuura Lan Xiang Jianhua Qi |
| author_facet | Yanan Liu Qian Liu Danni Chen Akira Matsuura Lan Xiang Jianhua Qi |
| author_sort | Yanan Liu |
| collection | DOAJ |
| description | In the present study, replicative lifespan and chronological lifespan assays of yeast were used to double-screen antiaging compounds from <i>Gentiana rigescens</i> Franch, a Chinese herb medicine. Inokosterone from <i>G. rigescens</i> Franch extended not only the replicative lifespan of K6001 yeast but also the chronological lifespan of YOM36 yeast. Furthermore, it can enhance the survival ability of mammalian cells. In order to understand the mechanism of action of this compound, this study focused on antioxidative stress and autophagy when performing the analysis. The increased cell survival rate under oxidative stress conditions, antioxidant enzyme activity and gene expression were observed in the inokosterone-treated groups. Meanwhile, the reactive oxygen species (ROS) and lipid peroxidation of yeast were obviously decreased. Additionally, the macroautophagy and mitophagy in YOM38-GFP-ATG8 yeast were increased upon inokosterone treatment, respectively. At the same time, the cleavage-free GFP from GFP-ATG8 in the cytoplasm and the ubiquitin of the mitochondria at the protein level were markedly enhanced after incubation with inokosterone. Furthermore, we investigated the effect of inokosterone on antioxidative stress and autophagy in mammalian cells, and the relationship between ROS and autophagy. The ROS, malondialdehyde (MDA) were significantly decreased, and the autophagosomes in mammalian cells were obviously increased after inokosterone treatment. The autophagosomes in ∆<i>sod1</i> yeast with a K6001 background had no obvious changes, and the ROS and MDA of ∆<i>sod1</i> yeast were increased compared with K6001 yeast. The increase of autophagosomes and the reduction of ROS and MDA in ∆<i>sod1</i> yeast were observed after treatment with inokosterone. Meanwhile, the reduction of the ROS level and the increase of the <i>SOD1</i> gene expression of K6001 yeast lacking autophagy were observed after treatment with inokosterone. In order to indicate whether the genes related to antioxidant enzymes and autophagy were involved in the antiaging effect of inokosterone, mutants of K6001 yeast were constructed to conduct a lifespan assay. The replicative lifespans of ∆<i>sod1</i>, ∆<i>sod2</i>, ∆<i>uth1</i>, ∆<i>skn7</i>, ∆<i>gpx</i>, ∆<i>cat</i>, ∆<i>atg2</i>, and ∆<i>atg32</i> of K6001 yeast were not affected by inokosterone. These results suggest that inokosterone exerted an antiaging activity via antioxidative stress and increased autophagy activation; autophagy affected the ROS levels of yeast via the regulation of <i>SOD1</i> gene expression. |
| first_indexed | 2024-03-09T22:45:59Z |
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| language | English |
| last_indexed | 2024-03-09T22:45:59Z |
| publishDate | 2022-01-01 |
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| spelling | doaj.art-f0134b7ba68549cc8dd0d3c38a837d552023-11-23T18:30:12ZengMDPI AGAntioxidants2076-39212022-01-0111221410.3390/antiox11020214Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy InductionYanan Liu0Qian Liu1Danni Chen2Akira Matsuura3Lan Xiang4Jianhua Qi5College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, ChinaDepartment of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, JapanCollege of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, ChinaIn the present study, replicative lifespan and chronological lifespan assays of yeast were used to double-screen antiaging compounds from <i>Gentiana rigescens</i> Franch, a Chinese herb medicine. Inokosterone from <i>G. rigescens</i> Franch extended not only the replicative lifespan of K6001 yeast but also the chronological lifespan of YOM36 yeast. Furthermore, it can enhance the survival ability of mammalian cells. In order to understand the mechanism of action of this compound, this study focused on antioxidative stress and autophagy when performing the analysis. The increased cell survival rate under oxidative stress conditions, antioxidant enzyme activity and gene expression were observed in the inokosterone-treated groups. Meanwhile, the reactive oxygen species (ROS) and lipid peroxidation of yeast were obviously decreased. Additionally, the macroautophagy and mitophagy in YOM38-GFP-ATG8 yeast were increased upon inokosterone treatment, respectively. At the same time, the cleavage-free GFP from GFP-ATG8 in the cytoplasm and the ubiquitin of the mitochondria at the protein level were markedly enhanced after incubation with inokosterone. Furthermore, we investigated the effect of inokosterone on antioxidative stress and autophagy in mammalian cells, and the relationship between ROS and autophagy. The ROS, malondialdehyde (MDA) were significantly decreased, and the autophagosomes in mammalian cells were obviously increased after inokosterone treatment. The autophagosomes in ∆<i>sod1</i> yeast with a K6001 background had no obvious changes, and the ROS and MDA of ∆<i>sod1</i> yeast were increased compared with K6001 yeast. The increase of autophagosomes and the reduction of ROS and MDA in ∆<i>sod1</i> yeast were observed after treatment with inokosterone. Meanwhile, the reduction of the ROS level and the increase of the <i>SOD1</i> gene expression of K6001 yeast lacking autophagy were observed after treatment with inokosterone. In order to indicate whether the genes related to antioxidant enzymes and autophagy were involved in the antiaging effect of inokosterone, mutants of K6001 yeast were constructed to conduct a lifespan assay. The replicative lifespans of ∆<i>sod1</i>, ∆<i>sod2</i>, ∆<i>uth1</i>, ∆<i>skn7</i>, ∆<i>gpx</i>, ∆<i>cat</i>, ∆<i>atg2</i>, and ∆<i>atg32</i> of K6001 yeast were not affected by inokosterone. These results suggest that inokosterone exerted an antiaging activity via antioxidative stress and increased autophagy activation; autophagy affected the ROS levels of yeast via the regulation of <i>SOD1</i> gene expression.https://www.mdpi.com/2076-3921/11/2/214<i>Gentiana rigescens</i> Franchinokosteroneantiagingantioxidative stressROSmitophagy |
| spellingShingle | Yanan Liu Qian Liu Danni Chen Akira Matsuura Lan Xiang Jianhua Qi Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction Antioxidants <i>Gentiana rigescens</i> Franch inokosterone antiaging antioxidative stress ROS mitophagy |
| title | Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction |
| title_full | Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction |
| title_fullStr | Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction |
| title_full_unstemmed | Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction |
| title_short | Inokosterone from <em>Gentiana rigescens</em> Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction |
| title_sort | inokosterone from em gentiana rigescens em franch extends the longevity of yeast and mammalian cells via antioxidative stress and mitophagy induction |
| topic | <i>Gentiana rigescens</i> Franch inokosterone antiaging antioxidative stress ROS mitophagy |
| url | https://www.mdpi.com/2076-3921/11/2/214 |
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