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

Xiao-Feng He,Ming-Feng Guo,Zheng Dai,Long Zhang,Con-Ran Zhao,Chun-Hua Zhang,Heng Li,Guo-Feng Tian,Fu-Ge Sui,Ling-Fei Zhang

doi:10.17305/bjbms.2017.2596

Abstract

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.

Highlights

Aging is the process of physical deterioration of the body and can be accompanied by various diseases, including osteopo‐ rosis, arthritis, cardiovascular atherosclerosis, Alzheimer’s dis‐ ease, and malignant tumors
The treat‐ ment with berberine increased the bone mineral density (BMD) to some extent in 3 berberine‐treated groups compared to the osteoporosis group, the BMD did not reach the normal values in these groups [Table 2]
The changes in the expression of OPG and receptor activator of nuclear factor kappa‐B ligand (RANKL) between the osteoporosis and berberine‐treated groups were consid‐ erable, especially in the group treated with the highest dose of berberine, where the differences in the OPG and RANKL expressions were statistically significant compared to the oste‐ oporosis group. These results indicate that OPG and RANKL are associated with the mechanism of action of berberine in rats with osteoporosis

Summary

Introduction

Aging is the process of physical deterioration of the body and can be accompanied by various diseases, including osteopo‐ rosis, arthritis, cardiovascular atherosclerosis, Alzheimer’s dis‐ ease, and malignant tumors. Submitted: 31 May 2017/Accepted: 13 July 2017 in China as well as in the whole world, common diseases related to old age, such as osteoporosis, have been causing widespread concern. As a systemic metabolic disease, osteoporosis causes microarchitectural deterioration of bone tissue, leading to increased bone fragility and risk of bone fractures. In China, the prevalence of osteoporosis in adults over 40 years old is about 13.2% [1], which is associated with increased medical costs. Different factors contribute to the onset of osteoporo‐ sis, including genetic, nutritional, and lifestyle factors among others [2,3].

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