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 (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.

A New Geniposidic Acid Derivative Exerts Antiaging Effects through Antioxidative Stress and Autophagy Induction.

Two compounds that can prolong the replicative lifespan of yeast, geniposidic acid (Compound 1) and geniposide (Compound 2), were isolated from Gardenia jasminoides Ellis. Compared with Compound 1, Compound 2 was different at C11 and showed better bioactivity. On this basis, seven new geniposidic derivatives (3-9) were synthesized. Geniposidic 4-isoamyl ester (8, GENI), which remarkably prolonged the replicative and chronological lifespans of K6001 yeast at 1 µM, was used as the lead compound. Autophagy and antioxidative stress were examined to clarify the antiaging mechanism of GENI. GENI increased the enzymes activities and gene expression levels of superoxide dismutase (SOD) and reduced the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) to improve the survival rate of yeast under oxidative stress. In addition, GENI did not extend the replicative lifespan of ∆sod1, ∆sod2, ∆uth1, ∆skn7, ∆cat, and ∆gpx mutants with K6001 background. The free green fluorescent protein (GFP) signal from the cleavage of GFP-Atg8 was increased by GENI. The protein level of free GFP showed a considerable increase and was time-dependent. Furthermore, GENI failed to extend the replicative lifespans of ∆atg32 and ∆atg2 yeast mutants. These results indicated that antioxidative stress and autophagy induction were involved in the antiaging effect of GENI.

Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress.

In the present study, the replicative lifespan assay of yeast was used to guide the isolation of antiaging substance from Gentiana rigescens Franch, a traditional Chinese medicine. A compound with antiaging effect was isolated, and the chemical structure of this molecule as amarogentin was identified by spectral analysis and compared with the reported data. It significantly extended the replicative lifespan of K6001 yeast at doses of 1, 3, and 10 µM. Furthermore, amarogentin improved the survival rate of yeast under oxidative stress by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and these enzymes' gene expression. In addition, this compound did not extend the replicative lifespan of sod1, sod2, uth1, and skn7 mutants with K6001 background. These results suggested that amarogentin exhibited antiaging effect on yeast via increase of SOD2, CAT, GPx gene expression, enzyme activity, and antioxidative stress. Moreover, we evaluated antioxidant activity of this natural products using PC12 cell system, a useful model for studying the nervous system at the cellular level. Amarogentin significantly improved the survival rate of PC12 cells under H2O2-induced oxidative stress and increased the activities of SOD and SOD2, and gene expression of SOD2, CAT, GPx, Nrf2, and Bcl-x1. Meanwhile, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) of PC12 cells were significantly reduced after treatment of the amarogentin. These results indicated that antioxidative stress play an important role for antiaging and neuroprotection of amarogentin. Interestingly, amarogentin exhibited neuritogenic activity in PC12 cells. Therefore, the natural products, amarogentin from G. rigescens with antioxidant activity could be a good candidate molecule to develop drug for treating neurodegenerative diseases.

Novel Anti-Aging Benzoquinone Derivatives from Onosma bracteatum Wall.

The aim of this study was to investigate anti-aging molecules from Onosma bracteatum Wall, a traditional medicinal plant used in the Unani and Ayurvedic systems of medicine. During bioassay-guided isolation, two known benzoquinones, allomicrophyllone (1) and ehretiquinone (2) along with three novel benzoquinones designated as ehretiquinones B-D (3-5) were isolated from O. bracteatum. Their structures were characterized by spectroscopic analysis through 1D and 2D NMR, by MS spectroscopic analysis and comparing with those reported in the literatures. The anti-aging potential of the isolated benzoquinones was evaluated through a yeast lifespan assay, and the results indicated that 1, 2, 4 and 5 significantly extended the replicative lifespan of K6001 yeast, indicating that these benzoquinones obtained from O. brateatum have the ability to be employed as a potential therapeutic agent against age-related diseases.