Application of SaintGSE to evaluate effects of Senna obtusifolia L. extract and obtusifolin on osteoarthritis-related gene pathways

SaintGSE, a supervised prediction tool using an autoencoder with the SAINT model, was employed to explore gene-pathway relationships based on fold changes from large differentially expressed gene (DEG) datasets. The study was applied to osteoarthritis (OA), a condition characterized by cartilage degradation and inflammation. SaintGSE was used to establish an independent criterion based on mutual gene expression changes.We compared four DEG samples in mouse chondrocytes treated under different conditions: 1) Interleukin (IL)-1beta (1 ng/mL), 2) IL-1beta (1 ng/mL) co-treated with S. obtusifolia L. extract (100 ug/mL), and 3) IL-1beta (1 ng/mL) co-treated with obtusifolin (200 ug/mL), to evaluate the effects of S. obtusifolia L. extract and obtusifolin on OA.Obtusifolin, an anthraquinone isolated from S. obtusifolia L., has been shown in our previous studies to alleviate OA symptoms. We hypothesized that the natural extract would regulate more OA-related pathways compared to the isolated compound obtusifolin. Results from SaintGSE suggested that the extract had broader effects on OA-related pathways than obtusifolin alone. In vitro studies confirmed the regulation of the NF-kappaB and P38 pathways, downregulation of catabolic factors (Mmp3, Mmp13, and Cox2), and cartilage recovery in OA-induced mice.