Abstract
Gentiopicroside (GPS), an antiaging secoiridoid glycoside, was isolated from Gentiana rigescens Franch, a traditional Chinese medicine. It prolonged the replicative and chronological lifespans of yeast. Autophagy, especially mitophagy, and antioxidative stress were examined to clarify the mechanism of action of this compound. The free green fluorescent protein (GFP) signal from the cleavage of GFP-Atg8 and the colocation signal of MitoTracker Red CMXRos and GFP were increased upon the treatment of GPS. The free GFP in the cytoplasm and free GFP and ubiquitin of mitochondria were significantly increased at the protein levels in the GPS-treated group. GPS increased the expression of an essential autophagy gene, ATG32 gene, but failed to extend the replicative and chronological lifespans of ATG32 yeast mutants. GPS increased the survival rate of yeast under oxidative stress condition; enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase; and decreased the levels of reactive oxygen species and malondialdehyde. The replicative lifespans of Δsod1, Δsod2, Δuth1, and Δskn7 were not affected by GPS. These results indicated that autophagy, especially mitophagy, and antioxidative stress are involved in the antiaging effect of GPS.
Highlights
Aging is a time-dependent functional decline that is the primary risk factor for many diseases [1, 2], such as Alzheimer’s disease, Parkinson’s disease, and diabetes
These results indicated that GPS can significantly prolong the replicative lifespan of K6001 yeast cells at concentrations of 1, 3, and 10 μM (p < 0:01, p < 0:05, and p < 0:05), respectively
The chronological lifespan assay of YOM36 yeast was performed to evaluate the antiaging activity of GPS
Summary
Aging is a time-dependent functional decline that is the primary risk factor for many diseases [1, 2], such as Alzheimer’s disease, Parkinson’s disease, and diabetes. Gentiana rigescens (G. rigescens) grows in the southwest region of China The roots of this Chinese herb medicine have been used to treat inflammation, hepatitis, and functional dyspepsia [5]. The mixture of gentisides (n-GS) was confirmed to have alleviation effects on the impaired memory of scopolamine-induced mouse model by inhibiting acetylcholinesterase activities and antioxidative stress and regulating the insulin-like growth factor 1 receptor/extracellular signal-regulated kinase (IGF-1R/ERK) signal pathway [8]. These results possibly proved the cognition-improving effect of G. rigescens on the molecular basis, which was mentioned in Sheng Nong’s Herbal Classic
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