Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy

Gentirigeoside B (GTS B) is a dammaren-type triterpenoid glycoside isolated from <i>G. rigescens</i> Franch, a traditional Chinese medicinal plant. In the present study, the evaluation of the anti-aging effect and action mechanism analysis for this compound were conducted. GTS B signific...

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Main Authors: Lan Xiang, Dejene Disasa, Yanan Liu, Rui Fujii, Mengya Yang, Enchan Wu, Akira Matsuura, Jianhua Qi
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/12/2373
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author Lan Xiang
Dejene Disasa
Yanan Liu
Rui Fujii
Mengya Yang
Enchan Wu
Akira Matsuura
Jianhua Qi
author_facet Lan Xiang
Dejene Disasa
Yanan Liu
Rui Fujii
Mengya Yang
Enchan Wu
Akira Matsuura
Jianhua Qi
author_sort Lan Xiang
collection DOAJ
description Gentirigeoside B (GTS B) is a dammaren-type triterpenoid glycoside isolated from <i>G. rigescens</i> Franch, a traditional Chinese medicinal plant. In the present study, the evaluation of the anti-aging effect and action mechanism analysis for this compound were conducted. GTS B significantly extended the replicative lifespan and chronological lifespan of yeast at doses of 1, 3 and 10 μM. Furthermore, the inhibition of Sch9 and activity increase of Rim15, Msn2 proteins which located downstream of TORC1 signaling pathway were observed after treatment with GTS B. Additionally, autophagy of yeast was increased. In addition, GTS B significantly improved survival rate of yeast under oxidative stress conditions as well as reduced the levels of ROS and MDA. It also increased the gene expression and enzymatic activities of key anti-oxidative enzymes such as Sod1, Sod2, Cat and Gpx. However, this molecule failed to extend the lifespan of yeast mutants such as ∆<i>cat</i>, ∆<i>gpx</i>, ∆<i>sod1</i>, ∆<i>sod2</i>, ∆<i>skn7</i> and ∆<i>uth1</i>. These results suggested that GTS B exerts an anti-aging effect via inhibition of the TORC1/Sch9/Rim15/Msn signaling pathway and enhancement of autophagy. Therefore, GTS B may be a promising candidate molecule to develop leading compounds for the treatment of aging and age-related disorders.
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spelling doaj.art-c0c30e7ddab547c582a89e664b19a3bb2023-11-24T12:56:58ZengMDPI AGAntioxidants2076-39212022-11-011112237310.3390/antiox11122373Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and AutophagyLan Xiang0Dejene Disasa1Yanan Liu2Rui Fujii3Mengya Yang4Enchan Wu5Akira Matsuura6Jianhua Qi7College of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou 310058, ChinaCollege of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou 310058, ChinaCollege of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou 310058, ChinaDepartment of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, JapanCollege of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou 310058, ChinaCollege of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou 310058, ChinaDepartment of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, JapanCollege of Pharmaceutical Science, Zhejiang University, 866 Yu Hang Road, Hangzhou 310058, ChinaGentirigeoside B (GTS B) is a dammaren-type triterpenoid glycoside isolated from <i>G. rigescens</i> Franch, a traditional Chinese medicinal plant. In the present study, the evaluation of the anti-aging effect and action mechanism analysis for this compound were conducted. GTS B significantly extended the replicative lifespan and chronological lifespan of yeast at doses of 1, 3 and 10 μM. Furthermore, the inhibition of Sch9 and activity increase of Rim15, Msn2 proteins which located downstream of TORC1 signaling pathway were observed after treatment with GTS B. Additionally, autophagy of yeast was increased. In addition, GTS B significantly improved survival rate of yeast under oxidative stress conditions as well as reduced the levels of ROS and MDA. It also increased the gene expression and enzymatic activities of key anti-oxidative enzymes such as Sod1, Sod2, Cat and Gpx. However, this molecule failed to extend the lifespan of yeast mutants such as ∆<i>cat</i>, ∆<i>gpx</i>, ∆<i>sod1</i>, ∆<i>sod2</i>, ∆<i>skn7</i> and ∆<i>uth1</i>. These results suggested that GTS B exerts an anti-aging effect via inhibition of the TORC1/Sch9/Rim15/Msn signaling pathway and enhancement of autophagy. Therefore, GTS B may be a promising candidate molecule to develop leading compounds for the treatment of aging and age-related disorders.https://www.mdpi.com/2076-3921/11/12/2373<i>G. rigescens</i> FranchGentirigeoside BTORC1 signaling pathwayautophagyoxidative stresslongevity
spellingShingle Lan Xiang
Dejene Disasa
Yanan Liu
Rui Fujii
Mengya Yang
Enchan Wu
Akira Matsuura
Jianhua Qi
Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy
Antioxidants
<i>G. rigescens</i> Franch
Gentirigeoside B
TORC1 signaling pathway
autophagy
oxidative stress
longevity
title Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy
title_full Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy
title_fullStr Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy
title_full_unstemmed Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy
title_short Gentirigeoside B from <i>Gentiana rigescens</i> Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy
title_sort gentirigeoside b from i gentiana rigescens i franch prolongs yeast lifespan via inhibition of torc1 sch9 rim15 msn signaling pathway and modification of oxidative stress and autophagy
topic <i>G. rigescens</i> Franch
Gentirigeoside B
TORC1 signaling pathway
autophagy
oxidative stress
longevity
url https://www.mdpi.com/2076-3921/11/12/2373
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