| Objective To study whether icariin can antagonize bone loss induced by simulated microgravity in rats and to explore its mechanism, so as to lay a foundation for the development of anti-space microgravity bone loss drugs derived from Chinese herbal medicine. Methods Thirty 2-month-old Wistar male rats were randomly divided into three groups: control group (CON), tail-hanger group (HLS), and icariside group (ICA), with 10 rats in each group. The tail-hanger model was established in both HLS and ICA groups. Rats in ICA group received 50 mg/kg icariside, while rats in CON and HLS groups received an equal volume of distilled water only. After 28 days of administration, all rats were executed. The left femurs and lumbar vertebrae were placed in a micro-CT scanner for bone microstructure analysis and 3D reconstruction. The arterial blood was extracted from the abdominal aorta of rats. The serum was separated and the contents of PINP, CTX-1, OPG, RANKL, 8-iso-PGF2α, and 8-OHdG were determined using ELISA. The total protein was extracted from the right tibia. The expression levels of BMP2, COL-1, OSX, and Runx2 were analyzed using Western blotting method. The MDA content in serum was measured with TBA method. The SOD activity in serum was measured with WST-1 method. Results (1) The results of micro-CT scan analysis showed that compared to the CON group, the distribution of bone trabeculae was sparse in the HLS group, while the ICA group was significantly better than the HLS group and close to the CON group. BMD, BS/TV, BV/TV, Tb.N, and Tb.Th were lower (P<0.05) and Tb.Sp was higher (P<0.05) in the HLS group compared to the CON group. BMD, BS/TV, BV/TV, Tb.N, and Tb.Th were significantly higher (P<0.05) in the ICA group compared to the HLS group, while Tb.Sp was significantly lower (P<0.05). The trabeculae of the fourth lumbar vertebra and their quantification results were consistent with those of the femur. (2) The changes of serum bone metabolic indexes showed that the bone formation indexes PINP and OPG were significantly lower in the HLS group than in the CON group (P<0.05), while the bone resorption indexes CTX-1 and RANKL were higher than in the CON group (P<0.05). The levels of PINP and OPG were significantly higher in the ICA group than in the HLS group (P<0.05), CTX-1 and RANKL were significantly lower than those in the HLS group (P<0.05), with the levels of PINP, OPG and CTX-1 similar to those in the CON group. (3) The expression levels of bone formation proteins BMP2, Runx2, COL-1, and OSX in tibial bone tissue were lower in the HLS group than in the CON group. The expression levels of BMP2, Runx2, COL-1, and OSX were higher in the ICA group than in the HLS group, with Runx2 and OSX expression levels similar to those in the CON group. (4) The results of oxidative and antioxidant indexes showed that compared to the CON group, the serum levels of 8-iso-PGF2α, 8-OHdG, and MDA increased (P<0.05) and the SOD enzyme activity decreased (P<0.05) in the HLS group. The serum levels of 8-iso-PGF2α, 8-OHdG, and MDA decreased (P<0.05) and the SOD enzyme activity increased (P<0.05) in the ICA group compared to the HLS group. Conclusion The simulated microgravity environment causes a decrease in bone mineral density, a decrease in maximum load, and a degradation of bone microstructure. Icariin promotes bone formation, inhibits bone resorption, reduces the degree of oxidation in vivo, and enhances antioxidant capacity thus effectively preventing bone loss due to oxidative stress in rats. |