Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages

•AS-IV repolarizes macrophages from M1 to M2 phenotypes.•Culture medium from AS-IV treated M1 macrophages suppresses cell apoptosis.•AS-IV decreases the ratio of M1 macrophages in the femoral head. Osteonecrosis of the femoral head (ON-FH) is a common complication of steroid use. Pro-inflammatory macrophages play a crucial role in the apoptosis of osteocytes. The objective of the study was to evaluate a plant extract astragaloside IV (AS-IV) in treating ON-FN. Bone-marrow-derived macrophages (BMDMs) were treated with lipopolysaccharides (LPS), IFN-γ or IL-4 to induce M1 and M2-like phenotypes. Quantitative real-time PCR and Western blot were used to examine M1 and M2 phenotypic markers. Flow cytometry was used to analyze MHC II, CD206, F4/80, and CD11b levels and cell apoptosis. Glucocorticoid was used to induce ON-FN in mice. TNF-α and IL-1β levels in femoral head were determined using enzyme-linked immunosorbent assay. AS-IV repolarized macrophages from M1 to M2 phenotypes. Culture medium from AS-IV treated M1 macrophages induced less cell apoptosis osteocytes compared to that from untreated M1 macrophages. In ON-FH mice, the ratio of M1 macrophages was decreased in the femoral head by AS-IV, concomitant with a decrease in TNF-α and IL-1β levels. AS-IV is effective in alleviating ON-FH through its effects in repolarizing macrophages from M1-like phenotype to M2-like phenotype, promoting survival of osteocytes, reducing arthritic symptoms, and decreasing inflammatory cytokines.