Berberine alleviates oxidative stress in rats with osteoporosis through receptor activator of NF-κB/receptor activator of NF-κBligand/osteoprotegerin (RANK/RANKL/OPG) pathway

Previous studies suggested that oxidative stress is related to the onset and development of osteoporosis. Moreover, it was demonstrated that berberine has a protective effect against oxidative stress-induced injuries. In this study, we aimed to investigate the effect and mechanism of action of berberine on rats with induced osteoporosis. Sixty 8-week-old female Wistar rats were randomly divided into the following 6 groups: control saline-treated, osteoporosis saline-treated, 3 osteoporosis berberine-treated groups (Ber 5, 10, and 20 mg/kg/body weight, respectively), and osteoporosis alendronate-treated (ALD) group. Osteoporosis was induced by bilateral ovariectomy. All treatments were performed for 8 weeks. The bone mineral density (BMD), serum alkaline phosphatase (ALP), osteocalcin, calcium, phosphorus, superoxide dismutase (SOD), methylenedioxyamphetamine (MDA), and glutathione peroxidase (GSH-Px) level was determined in the rat femur tissue. The gene and protein expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) was analyzed by quantitative reverse transcription PCR and Western blot, respectively. The BMD, SOD and GSH-Px levels, and the expression of OPG were significantly lower in osteoporosis compared to control group (all P < 0.05). The serum levels of osteocalcin, ALP, and MDA, and the expression of RANKL were significantly higher in osteoporosis compared to control group (all P < 0.05). Berberine, especially the high doses of berberine, effectively increased SOD, GSH-Px, and OPG levels as well as decreased serum osteocalcin, ALP, MDA and RANKL levels in berberine-treated osteoporosis groups (all P < 0.05). To conclude, oxidative stress may promote the development of osteoporosis in rats through the RANK/RANKL/OPG pathway. The antioxidative effect of berberine reduces the development of osteoporosis in rats to some extent.