Ginsenoside Prolongs the Lifespan of C. elegans via Lipid Metabolism and Activating the Stress Response Signaling Pathway

Panax ginsengis a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides fromPanax ginseng, on the lifespan ofCaenorhabditis elegans(C. elegans). We found that TG extended the lifespan ofC. elegansand reduced lipofuscin accumulation. Moreover, TG increased the survival ofC. elegansin response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression ofnrh-80,daf-12,daf-16,hsf-1and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan ofdaf-16andhsf-1mutants, highlighting their role in the antiaging effects of TG inC. elegans. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg1, Rg2and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan ofC. elegansto levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside inC. elegans.Keywords:Panax ginseng;lifespan;lipid metabolism;stress-resistant;Caenorhabditis elegans