Gentirigeoside B from Gentiana rigescens Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy.
Gentirigeoside B from Gentiana rigescens Franch Prolongs Yeast Lifespan via Inhibition of TORC1/Sch9/Rim15/Msn Signaling Pathway and Modification of Oxidative Stress and Autophagy.
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来自 Gentiana rigescens Franch 的 Gentirigeoside B 通过抑制 TORC1/Sch9/Rim15/Msn 信号通路以及改变氧化应激和自噬来延长酵母寿命
DOI：
10.3390/antiox11122373
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发表时间：
2022-11-30
期刊：
影响因子：
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中科院分区：
文献类型：
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龙胆皂苷B （gentirigoside B, GTS B）是从中药植物龙胆皂苷中分离得到的一种损伤型三萜苷类化合物。本研究对该化合物的抗衰老作用进行了评价，并对其作用机理进行了分析。GTS B在1、3和10 μM剂量下显著延长酵母的复制寿命和时间寿命。经GTS b处理后，发现TORC1信号通路下游的Sch9蛋白受到抑制，Rim15、Msn2蛋白活性增加，酵母自噬增强。此外，GTS B显著提高了酵母在氧化应激条件下的存活率，降低了ROS和MDA的水平。提高了Sod1、Sod2、Cat、Gpx等关键抗氧化酶的基因表达和酶活性。然而，该分子未能延长如∆cat、∆gpx、∆sod1、∆sod2、∆skn7和∆uth1等酵母突变体的寿命。这些结果表明，GTS B通过抑制TORC1/Sch9/Rim15/Msn信号通路和增强自噬来发挥抗衰老作用。因此，GTS B可能是开发治疗衰老和年龄相关疾病的先导化合物的有希望的候选分子。
Gentirigeoside B (GTS B) is a dammaren-type triterpenoid glycoside isolated from G. rigescens 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 ∆cat, ∆gpx, ∆sod1, ∆sod2, ∆skn7 and ∆uth1. 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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