Artemisiae Scopariae Herba (Yinchen) suppresses ferroptosis in mice with osteoporosis via the Nrf2/Slc7a11/Gpx4 pathway

With the aging of the population, the incidence of postmenopausal osteoporosis (PMOP) is increasing. Extracts from Artemisiae Scopariae Herba, also known as Yinchen (YC), promote osteogenic differentiation and bone formation; however, the specific mechanism is unclear. The present study aimed to investigate the effects and mechanism of YC on PMOP. Ultra‑performance liquid chromatography‑tandem mass spectrometry was used to determine the potential predominant components of YC, and an ovariectomized (OVX) mouse model was established to evaluate the effects of YC on PMOP and its potential mechanisms. Initially, the therapeutic effect of YC on PMOP was assessed by micro‑CT bone analysis, pathological observation and ELISA detection. Combined with serum ELISA, reverse transcription‑quantitative PCR and immunohistochemical staining, the potential key anti‑PMOP pathway of YC was explored. A total of 2,072 compounds were identified in YC. The main active components of YC included chlorogenic acid, ferulic acid and caffeic acid. Experimental studies provided evidence that YC may improve bone loss and bone microstructure deterioration caused by ovariectomy. YC treatment also upregulated serum estrogen levels, and the expression of osteoprotegerin, runt‑related transcription factor 2 and glutathione peroxidase 4 (Gpx4) in bone tissue. Ovariectomy led to abnormal iron metabolism and increase the accumulation of lipid peroxides. YC reduced liver iron deposition, restored glutathione levels, and downregulated serum tartrate‑resistant acid phosphatase, osteocalcin, ferritin and hepcidin levels in mice. In addition, YC reversed the decreased expression of nuclear factor erythroid 2‑related factor 2 (Nrf2), solute carrier family 7 member 11 (Slc7a11) and Gpx4 in the bone tissues of OVX mice. In conclusion, the present study suggested the effectiveness of YC in potentially reducing ovariectomy‑induced osteoporosis in mice. YC promoted bone formation and improved bone microstructure, potentially by inhibiting ferroptosis via activation of the Nrf2/Slc7a11/Gpx4 pathway in OVX mice.