Calycosin prevents IL-1β-induced articular chondrocyte damage in osteoarthritis through regulating the PI3K/AKT/FoxO1 pathway.

Osteoarthritis (OA) is a joint disorder that is associated with chondrocyte damage under inflammatory environment. Calycosin is an astragalus extract with potential anti-inflammatory and anti-tumor activities. The purpose of this research is to explore the activity and mechanism of calycosin in interleukin-1beta (IL-1β)-induced chondrocyte injury. In the present study, the targets of calycosin and OA were analyzed according to HERB, DisGeNet, String, GO terms, and KEGG pathway enrichment assays. Human primary chondrocytes were treated with calycosin, and stimulated with IL-1β. Cell viability was detected by CCK-8 assay. Cell apoptosis was investigated by flow cytometry, and caspase-3 activity analyses. Inflammation was analyzed according to inflammatory cytokines levels by enzyme-linked immunosorbent assay (ELISA). The proteins associated with extracellular matrix (ECM) degradation and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box O1 (FoxO1) signaling pathways were measured using Western blotting. The results showed that total of 25 overlapping targets of calycosin against OA were predicted. These targets might drive the FoxO pathway. Calycosin alone induced little cytotoxicity to chondrocytes, and it alleviated IL-1β-induced viability inhibition, cell apoptosis, inflammatory cytokine secretion, and ECM degradation in chondrocytes. Calycosin repressed IL-1β-induced activation of the PI3K/AKT/FoxO1 signaling. Activation of the PI3K/AKT/FoxO1 signaling mitigated the suppressive effect of calycosin on chondrocyte apoptosis, inflammation, and ECM degradation induced by IL-1β. As a conclusion, calycosin prevents IL-1β-induced chondrocyte apoptosis, inflammation, and ECM degradation through inactivating the PI3K/AKT/FoxO1 pathway.