Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors
1,2,3,4,6-penta-<i>O</i>-galloyl-β-D-glucose (PGG) is the main phenolic active ingredient in <i>Paeoniae Radix Alba</i>, which is commonly used for the treatment of osteoporosis (OP). PGG is a potent natural antioxidant, and its effects on OP remain unknown. This study aimed...
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2024-10-01
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| author | Yongqing Hua Haili Wang Tingting Chen Yeru Zhou Zhiyuan Chen Xinyue Zhao Shaoqin Mo Hongyun Mao Miao Li Linxia Wang Min Hong |
| author_facet | Yongqing Hua Haili Wang Tingting Chen Yeru Zhou Zhiyuan Chen Xinyue Zhao Shaoqin Mo Hongyun Mao Miao Li Linxia Wang Min Hong |
| author_sort | Yongqing Hua |
| collection | DOAJ |
| description | 1,2,3,4,6-penta-<i>O</i>-galloyl-β-D-glucose (PGG) is the main phenolic active ingredient in <i>Paeoniae Radix Alba</i>, which is commonly used for the treatment of osteoporosis (OP). PGG is a potent natural antioxidant, and its effects on OP remain unknown. This study aimed to investigate the effects of PGG on promoting bone formation and explore its estrogen receptor (ER)-related mechanisms. A hydrogen peroxide-induced osteoblast apoptosis model was established in MC3T3-E1 cells. The effects of PGG were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, alkaline phosphatase (ALP) staining, RT-qPCR, and Western blot methods. Furthermore, a prednisolone-induced zebrafish OP model was employed to study the effects in vivo. ER inhibitors and molecular docking methods were used further to investigate the interactions between PGG and ERs. The results showed that PGG significantly enhanced cell viability and decreased cell apoptosis by restoring mitochondrial function, attenuating reactive oxygen species levels, decreasing the mitochondrial membrane potential, and enhancing ATP production. PGG enhanced ALP expression and activity and elevated osteogenic differentiation. PGG also promoted bone formation in the zebrafish model, and these effects were reversed by ICI182780. These results provide evidence that the effects of PGG in alleviating apoptosis and promoting bone formation may depend on ERs. As such, PGG is considered a valuable candidate for treating OP. |
| format | Article |
| id | doaj-art-d7a977cae31a42f496678ffc1a332f4e |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-d7a977cae31a42f496678ffc1a332f4e2024-11-08T14:38:22ZengMDPI AGMolecules1420-30492024-10-012921511010.3390/molecules29215110Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen ReceptorsYongqing Hua0Haili Wang1Tingting Chen2Yeru Zhou3Zhiyuan Chen4Xinyue Zhao5Shaoqin Mo6Hongyun Mao7Miao Li8Linxia Wang9Min Hong10Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China1,2,3,4,6-penta-<i>O</i>-galloyl-β-D-glucose (PGG) is the main phenolic active ingredient in <i>Paeoniae Radix Alba</i>, which is commonly used for the treatment of osteoporosis (OP). PGG is a potent natural antioxidant, and its effects on OP remain unknown. This study aimed to investigate the effects of PGG on promoting bone formation and explore its estrogen receptor (ER)-related mechanisms. A hydrogen peroxide-induced osteoblast apoptosis model was established in MC3T3-E1 cells. The effects of PGG were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, alkaline phosphatase (ALP) staining, RT-qPCR, and Western blot methods. Furthermore, a prednisolone-induced zebrafish OP model was employed to study the effects in vivo. ER inhibitors and molecular docking methods were used further to investigate the interactions between PGG and ERs. The results showed that PGG significantly enhanced cell viability and decreased cell apoptosis by restoring mitochondrial function, attenuating reactive oxygen species levels, decreasing the mitochondrial membrane potential, and enhancing ATP production. PGG enhanced ALP expression and activity and elevated osteogenic differentiation. PGG also promoted bone formation in the zebrafish model, and these effects were reversed by ICI182780. These results provide evidence that the effects of PGG in alleviating apoptosis and promoting bone formation may depend on ERs. As such, PGG is considered a valuable candidate for treating OP.https://www.mdpi.com/1420-3049/29/21/5110osteoporosisMC3T3-E1zebrafishestrogen receptor αnuclear factor erythroid 2-related factor 2reactive oxygen species |
| spellingShingle | Yongqing Hua Haili Wang Tingting Chen Yeru Zhou Zhiyuan Chen Xinyue Zhao Shaoqin Mo Hongyun Mao Miao Li Linxia Wang Min Hong Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors Molecules osteoporosis MC3T3-E1 zebrafish estrogen receptor α nuclear factor erythroid 2-related factor 2 reactive oxygen species |
| title | Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors |
| title_full | Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors |
| title_fullStr | Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors |
| title_full_unstemmed | Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors |
| title_short | Antioxidant 1,2,3,4,6-Penta-<i>O</i>-galloyl-β-D-glucose Alleviating Apoptosis and Promoting Bone Formation Is Associated with Estrogen Receptors |
| title_sort | antioxidant 1 2 3 4 6 penta i o i galloyl β d glucose alleviating apoptosis and promoting bone formation is associated with estrogen receptors |
| topic | osteoporosis MC3T3-E1 zebrafish estrogen receptor α nuclear factor erythroid 2-related factor 2 reactive oxygen species |
| url | https://www.mdpi.com/1420-3049/29/21/5110 |
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