Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway

Abstract

Context

Osteoporosis (OP) is a metabolic disease. We have previously demonstrated that aucubin (AU) has anti-OP effects that are due to its promotion of the formation of osteoblasts.

Objectives

To investigate the mechanisms of anti-OP effects of AU.

Materials and methods

C57BL/6 mice were randomly divided into control group, 30 mg/kg Dex-induced OP group (OP model group, 15 μg/kg oestradiol-treated positive control group, 5 or 45 mg/kg AU-treated group), and 45 mg/kg AU-alone-treated group. The administration lasted for 7 weeks. Subsequently, 1, 2.5 and 5 µM AU were incubated with 50 ng/mL RANKL-induced RAW264.7 cells for 7 days to observe osteoclast differentiation. The effect of AU was evaluated by analysing tissue lesions, biochemical factor and protein expression.

Results

The LD₅₀ of AU was greater than 45 mg/kg. AU increased the number of trabeculae and reduced the loss of chondrocytes in OP mice. Compared to OP mice, AU-treated mice exhibited decreased serum concentrations of TRAP5b (19.6% to 28.4%), IL-1 (12.2% to 12.6%), IL-6 (12.1%) and ROS (5.9% to 10.7%) and increased serum concentrations of SOD (14.6% to 19.4%) and CAT (17.2% to 27.4%). AU treatment of RANKL-exposed RAW264.7 cells decreased the numbers of multi-nuclear TRAP-positive cells, reversed the over-expression of TRAP5, NFATc1 and CTSK. Furthermore, AU increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins in RANKL-exposed RAW264.7 cells.

Conclusions

AU slows the development of OP via Nrf2-mediated antioxidant pathways, indicating the potential use of AU in OP therapy and other types of OP research.

Keywords:

• Natural active monomer
• metabolic bone disease
• reactive oxygen species

Author contributions

Min Hu and Di Wang designed the experiments. Yongfeng Zhang, Xin Liu, Yangyang Li, Minkai Song, Yutong Li, Anhui Yang, Yaqin Zhang performed the experiments. Yongfeng Zhang, Xin Liu, Min Hu, Di Wang analysed the data and wrote the manuscript.

Disclosure statement

The authors declare that there is no conflict of interest.

Data availability statement

All data generated and analysed during the study are included in this published article.

Additional information

Funding

This work was supported by the Science and Technology Research Project, Education Department of Jilin Province of China [No. JJKH20200322KJ], the Natural Science Foundation of China [No. 81870795], the Project from the Department of Health of Jilin Province [No. 2020Q022] and the Special Projects of Cooperation between Jilin University and Jilin Province [No. SXGJSFKT2020-1].