Shenrong Guben Huanshao Pill enhanced stress resistance and extended the lifespan of Caenorhabditis elegans by activating the oxidative stress system via the DAF-16/FOXO signaling pathway.

SRGBHSP is a classic traditional Chinese medicinal. Modern studies found that SRGBHSP had antioxidant, anti-inflammatory and constitution-strengthening pharmacological effects. Oxidative stress is a major factor that can cause an organism to age. Therefore, we proposed that SRGBHSP has an aging modulatory effect by its antioxidant properties. In the present study, we used a C. elegans model to explore the aging modulatory activity of the extract from SRGBHSP. Aging modulatory effects of SRGBHSP were determined by lifespan assays under normal and extreme conditions, as well as assays for body bending frequency and pharyngeal pumping rate. In vivo antioxidant activity of SRGBHSP was estimated through ROS, MDA levels and the activities of antioxidant enzymes. The mechanisms of aging modulatory effects of SRGBHSP were further investigated via qRT-PCR, nuclear translocation assay, transcriptomics and metabolomics analysis. SRGBHSP extends the lifespan of C. elegans and reduces the accumulation of oxidative metabolites. SRGBHSP upregulated the transcription of daf-16, promoted the nuclear translocation of DAF-16 and increased the transcription of downstream genes sod-3 and gst-4. KEGG enrichment analysis of the transcriptome identified the peroxisome pathway and the classical DAF-16/FOXO-dependent IIS longevity pathway. Metabolomics indicates that SRGBHSP primarily exerts its function by affecting the vitamin B6 metabolic pathway. The results of this study showed that SRGBHSP increased the activity of antioxidant enzyme in C. elegans and reduced the products of oxidative metabolism to prevent oxidative stress. Its aging modulatory effect is mainly produced through the activation of DAF-16/FOXO-dependent IIS signaling pathway and vitamin B6 metabolic pathway.