Involvement of the Sch9/Rim15/Msn2 signaling pathway in the anti-aging activity of dendrobine from Dendrobium nobile Lindl. via modification of oxidative stress and autophagy

Background Aging is an important pathogenic factor of age-related diseases and has brought huge health threat and economic burden to the society. Dendrobium nobile Lindl., a valuable herb in China, promotes longevity according to the record of ancient Chinese materia medica. This study aimed to discover the material basis of D. nobile as an anti-aging herb and elucidate its action mechanism. Methods K6001 yeast replicative lifespan assay was used to guide the isolation of D. nobile. The chronological lifespan assay of YOM36 yeast was further conducted to confirm the anti-aging activity of dendrobine. The mechanism in which dendrobine exerts anti-aging effect was determined by conducting anti-oxidative stress assay, quantitative real-time PCR, Western blot, measurements of anti-oxidant enzymes activities, determination of nuclear translocation of Rim15 and Msn2, and replicative lifespan assays of Δ sod1 , Δ sod2 , Δ cat , Δ gpx , Δ atg2 , Δ atg32 , and Δ rim15 yeasts. Results Under the guidance of K6001 yeast replicative lifespan system, dendrobine with anti-aging effect was isolated from D. nobile . The replicative and chronological lifespans of yeast were extended upon dendrobine treatment. In the study of action mechanism, dendrobine improved the survival rate of yeast under oxidative stress, decreased the levels of reactive oxygen species and malondialdehyde, and enhanced the enzyme activities and gene expression of superoxide dismutase and catalase, but it failed to elongate the replicative lifespans of Δ sod1 , Δ sod2 , Δ cat , and Δ gpx yeast mutants. Meanwhile, dendrobine enhanced autophagy occurrence in yeast but had no effect on the replicative lifespans of Δ atg2 and Δ atg32 yeast mutants. Moreover, the inhibition of Sch9 phosphorylation and the promotion of nuclear translocation of Rim15 and Msn2 were observed after treatment with denrobine. However, the effect of dendrobine disappeared from the Δ rim15 yeast mutant after lifespan extension, oxidative stress reduction, and autophagy enhancement. Conclusions Dendrobine exerts anti-aging activity in yeast via the modification of oxidative stress and autophagy through the Sch9/Rim15/Msn2 signaling pathway. Our work provides a scientific basis for the exploitation of D. nobile as an anti-aging herb.