Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway
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 d...
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2021
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oai:doaj.org-article:c2c32e70238846238bfb1338938c254f2021-11-11T14:23:41ZAucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway1388-02091744-511610.1080/13880209.2021.1996614https://doaj.org/article/c2c32e70238846238bfb1338938c254f2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1996614https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context 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.Yongfeng ZhangXin LiuYangyang LiMinkai SongYutong LiAnhui YangYaqin ZhangDi WangMin HuTaylor & Francis Grouparticlenatural active monomermetabolic bone diseasereactive oxygen speciesTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1556-1565 (2021) |
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natural active monomer metabolic bone disease reactive oxygen species Therapeutics. Pharmacology RM1-950 |
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natural active monomer metabolic bone disease reactive oxygen species Therapeutics. Pharmacology RM1-950 Yongfeng Zhang Xin Liu Yangyang Li Minkai Song Yutong Li Anhui Yang Yaqin Zhang Di Wang Min Hu Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway |
| description |
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. |
| format |
article |
| author |
Yongfeng Zhang Xin Liu Yangyang Li Minkai Song Yutong Li Anhui Yang Yaqin Zhang Di Wang Min Hu |
| author_facet |
Yongfeng Zhang Xin Liu Yangyang Li Minkai Song Yutong Li Anhui Yang Yaqin Zhang Di Wang Min Hu |
| author_sort |
Yongfeng Zhang |
| title |
Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway |
| title_short |
Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway |
| title_full |
Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway |
| title_fullStr |
Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway |
| title_full_unstemmed |
Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway |
| title_sort |
aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway |
| publisher |
Taylor & Francis Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/c2c32e70238846238bfb1338938c254f |
| work_keys_str_mv |
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