SuoquanYishen formula (SQYSF), a traditional Chinese herbal prescription for treating diabetic kidney disease (DKD), has demonstrated clinical efficacy in lowering blood glucose and alleviating renal damage. Emerging evidence implicates cellular senescence as a critical contributor to DKD progression. This study aimed to elucidate the mechanism by which SQYSF improves renal cellular senescence using both in vivo (db/db mice) and in vitro (high glucose-induced HK-2 cells) DKD models, with interventions involving SQYSF aqueous extract and SQYSF-containing serum. We screened 59 chemical compounds by UHPLC-QTOF-MS and used network pharmacology approach to discover that autophagy and cellular senescence are important pathways for pharmacological treatment of disease. Experimental validation demonstrated that senescence and damage occurred in the kidneys of db/db mice and HK-2 cells under high glucose environment, and SQYSF ameliorated these abnormal changes. Then, we also found that SQYSF enhanced autophagy in renal tissues and cells, whereas co-treatment with the autophagy inhibitor Bafilomycin A1 abolished SQYSF’s anti-senescence effects. Notably, DKD progression was associated with elevated Rubicon expression at mRNA and protein levels, accompanied by increased m6A modification. While SQYSF effectively downregulated Rubicon mRNA and protein expression, it did not influence m6A modification levels. Further investigation identified that SQYSF was able to target to reduce YTHDF1 expression level. Overexpression of YTHDF1 in HK-2 cells increased Rubicon mRNA stability and protein expression, while concurrently reversing SQYSF-induced autophagy enhancement and senescence amelioration. These results suggest that SQYSF exerts its role in ameliorating renal cellular senescence in DKD by targeting to reduce the expression level of YTHDF1, which inhibits the level of Rubicon mRNA and protein translation, and thus promotes autophagy. Our results reveal the active components and mechanisms of SQYSF for the treatment of DKD, which may provide useful information to guide the clinical application of SQYSF as well as the therapeutic pathway for DKD.

Paederia scandens (Lour.) Merr is a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects of paederoside (PSG) have not been thoroughly investigated; therefore, in this study, Caenorhabditis elegans (C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan of C. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant gene skn-1 and longevity-associated gene daf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited in C. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component of Paederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feeding C. elegans PSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug.

This study comprehensively employed network toxicology and experimental validation to systematically investigate the potential mechanisms by which triclosan (TCS) exacerbates rheumatoid arthritis (RA). Through multi-database screening, 173 common targets between TCS and RA were obtained. Combined with protein-protein interaction (PPI) network analysis and five machine learning algorithms, eight core hub genes (AR, CDKN1A, IGF1R, JAK2, JUN, MAPK8, MYC, and PARP1) were identified. Enrichment analysis indicated that TCS primarily interferes with signalling pathways, such as JAK-STAT, cellular senescence, and mitophagy. In vitro experiments demonstrated that TCS induces macrophage senescence and polarisation toward the M1 phenotype, promotes the expression of inflammatory cytokines, and inhibits mitophagy, leading to the accumulation of mitochondrial reactive oxygen species (ROS), loss of mitochondrial membrane potential, and impaired mitochondrial function, thereby exacerbating the inflammatory response. This study reveals that TCS may disrupt immune-metabolic homeostasis through multi-target, multi-pathway mechanisms to promote the onset and progression of RA, providing a new theoretical basis for understanding its environmental toxicity and for the prevention and treatment of RA.