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

Abstract

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.

Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

“…[81] In addition, gentirigeoside B inhibits Sch9 downstream of TORC1, increases Rim15 and Msn2 activities downstream of TORC1, and induces autophagy. [81] Therefore, gentirigeoside B may extend RLS and CLS by suppressing the TORC1 pathway via the downstream factors Sch9, Rim15, and Msn2. [81] Autophagy plays an important role in regulating the lifespan of various organisms, including the CLS of yeast.…”

“…[81] Therefore, gentirigeoside B may extend RLS and CLS by suppressing the TORC1 pathway via the downstream factors Sch9, Rim15, and Msn2. [81] Autophagy plays an important role in regulating the lifespan of various organisms, including the CLS of yeast. Suppressing the TORC1 pathway also contributes to autophagy induction.…”

“…Gentirigeoside B from Gentiana rigescens Franch increases RLS and CLS in S. cerevisiae . [ 81 ] In addition, gentirigeoside B inhibits Sch9 downstream of TORC1, increases Rim15 and Msn2 activities downstream of TORC1, and induces autophagy. [ 81 ] Therefore, gentirigeoside B may extend RLS and CLS by suppressing the TORC1 pathway via the downstream factors Sch9, Rim15, and Msn2.…”

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

“…Properly functional autophagy plays the role of adaptive quality control mechanism to alternations in nutrient availability and cellular stress (D. Park et al., 2016; Ploumi et al., 2023; Tuohetaerbaike et al., 2020). However, it could be accelerated by stress triggers such as CR, oxidative stress, endoplasmic reticulum stress, hypoxia, or inflammation (M. Wu et al., 2021; Xiang et al., 2022). Eventually, autophagy hyperactivation could lead to a dysregulated autophagy response and induce metabolic dysregulations, cellular senescence, and cell death (Yamamuro et al., 2020).…”

An Integrated Strategy for Investigating Antioxidants from Ribes himalense Royle ex Decne and Their Potential Target Proteins

“…Elucidating the chemical composition of traditional Chinese medicines has been the focus of researchers to enable their widespread utilization globally [ 7 ]. The isolation of high-purity compounds in traditional Chinese medicines is not only beneficial to their modern pharmacological studies, but also key to the in-depth exploration of drug–disease interaction mechanisms [ 8 , 9 ]. At present, numerous techniques have been developed based on the chromatography concept to analyze and separate chemical components in natural products, including as gas chromatography, liquid chromatography, and high-speed counter-current chromatography, among which liquid chromatography is the most widely used [ 10 , 11 , 12 , 13 ].…”