Artemisia annua L. extract alleviates glucocorticoid-induced osteoporosis by stimulating bone formation via...

Oxidative stress (OS) inhibits bone formation and contributes to bone loss in glucocorticoid-induced osteoporosis (GIOP). Artemisia annua L. (AA), an oxidative Chinese medicinal herb traditionally used to treat bone steaming and orthopedic diseases, has shown potential as an anti-osteoporotic agent. In this study, AA extract (AE) was administered to dexamethasone (Dex)-induced GIOP mice to investigate its anti-osteoporotic activity. AE effectively ameliorated bone loss, stimulated bone formation, and mitigated oxidative damage in GIOP mice. In MC3T3-E1 osteoblastic cells, AE rescued the Dex-impaired proliferation and osteogenic differentiation. AE also inhibited the accumulation of ROS and MDA, promoted the activity of CAT and SOD, and upregulated the expression of PGC-1α, Nrf2, HO-1, and SOD2. siRNA-mediated knockdown of PGC-1α or Nrf2 counteracted AE's regulatory effects on these antioxidant genes, concomitant with increased oxidative damage in transfected cells. An integrated analysis of virtual pharmacokinetic predictions, authentic pharmacokinetic data, and reported pharmacological effects suggested that luteolin was the principal contributor to the antioxidant and anti-osteoporotic activities of AE. In summary, AE promotes bone formation by improving Dex-injured osteoblast differentiation via the PGC-1α/Nrf2/HO-1/SOD2 pathway, indicating its potential as a therapeutic agent for GIOP and other OS-related orthopedic diseases.