| Residential College | false |
| Status | 已發表Published |
| Title | Studies on the anti-osteoporotic effects and molecular mechanisms of Glycine tabacina extract and coumestans |
| Author | TAN LIHUA 
|
| Subtype | 博士Phd |
| Thesis Advisor | Prof. HE CHENGWEI |
| Date Issued | 2024-07 |
| Degree Grantor | University of Macau |
| Place of Conferral | Taipa, Macau SAR |
| Degree Name | Doctor of Philosophy |
| Degree Discipline | Biomedical Sciences |
| Keyword | Glycine Tabacina Phaseol Glycyrol Osteoporosis Mechanisms |
| Abstract | Osteoporosis is an osteolytic disorder that results from an imbalance between osteoblast-driven osteogenesis and osteoclast-driven bone absorption. Hence, targeting bone formation and resorption is considered as a fundamental strategy for preventing or treating bone disorders effectively. The aim of this study is to examine the osteoprotective effect and underlying mechanisms of Glycine tabacina ethanol extract (GTE), phaseol (PHA), and glycyrol (GC) in vitro and in vivo. Firstly, our study provides comprehensive evidence supporting the potential therapeutic efficacy of GTE in mitigating osteoporosis by modulating bone metabolism, inflammation, osteoclast differentiation, and bone resorption activity. The influence of GTE on osteoclastogenesis is associated with its ability to block the activation of MAPK, estrogen and NF-κB pathways. Next, our findings indicate that PHA strongly facilitated osteoblast-driven osteogenesis, suppressed osteoclast-driven osteoclastogenesis and bone resorptive function, and mitigated LPS-induced inflammatory bone loss in mice. The impact of PHA on bone remodeling is linked to its ability to impede the formation of the TRAF6-TAK1 complex and the subsequent activation of TAK1, NF-κB, and MAPK pathways by targeting TAK1. Furthermore, we found that GC significantly alleviated LPS-induced osteoporosis in mice and DEX-induced osteoporosis in zebrafish. The cellular mechanisms underlying the anti-osteoporotic effect of GC involve the inhibition of osteoclast formation and the promotion of osteoblast differentiation. Studies on the molecular mechanisms uncovered that GC directly binds to the kinase domain of Syk and inhibits the activation of Syk and downstream PLCγ2/Ca2+/NFATc1 and MAPK pathways, thereby achieving dual regulation of osteoclastogenesis and osteogenesis, and ultimately alleviating the symptoms of osteoporosis. To the best of our understanding, this study is the first time to explore the anti-osteoporotic effects and the underlying mechanisms of GTE, PHA, and GC. The successful completion of this project provides compelling evidence supporting the potential development of GTE, PHA and GC as safe and effective agents or dietary supplements for the prevention and treatment of osteoporosis. |
| Document Type | Thesis |
| Collection | Institute of Chinese Medical Sciences |
| Recommended Citation GB/T 7714 | TAN LIHUA. Studies on the anti-osteoporotic effects and molecular mechanisms of Glycine tabacina extract and coumestans[D]. Taipa, Macau SAR, University of Macau, 2024. |
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| File Name/Size | Publications | Version | Access | License | ||
| PhD thesis-TAN LIHUA（12947KB） | 学位论文 | 开放获取 | CC BY-NC-SA | View Download | ||
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