Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Department of Applied Biology and Chemical Technology | en_US |
| dc.creator | Wong, Ka Chun | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/7221 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | - |
| dc.rights | All rights reserved | en_US |
| dc.title | Characterization of the osteoprotective flavan-3-ols from rhizoma drynariae | en_US |
| dcterms.abstract | Rhizome of Drynaria fortunei (Kunze) J. Sm. (DF) is a traditional Chinese herbal medicine commonly used to manage bone disease. Recent studies suggested that flavan-3-ols are the active ingredients in DF as they could stimulate the growth of osteoblastic cells. However, the mechanisms of how flavan-3-ols act on bone remain unclear. Therefore, the present study aimed to characterize the effects of DF flavan-3-ols on bone mechanisms. Synthetic flavan-3-ols were used in this study. Flavan-3-ols significantly increased the cell proliferation rate (P<0.05) of mature osteoblastic-like UMR-106 cells and these effects were blocked by estrogen receptor (ER) antagonist, ICI 182,780. Flavan-3-ols also increased the cell proliferation rate of estrogen sensitive human breast cancer MCF-7 cells significantly (P<0.05). Different flavan-3-ols could activate ER-α and ER-β mediated estrogen response element dependent transcription activities (P<0.05) differentially. Although the actions of flavan-3-ols were found to be ER mediated, there was not a direct binding between flavan-3-ols and ERs. (-)-Epiafzelechin was selected for the further characterization as it could promote the proliferation and differentiation rate of UMR-106 cells. (-)-Epiafzelechin could increase the alkaline phosphatase activities (P<0.05) and extracellular matrix collagen level (P<0.05) but not calcium deposition in murine preosteoblastic MC3T3-E1 cells. It also significantly increased the Cbfa2/Runx2, collagen 1a1 and osteocalcin (P<0.05) mRNA expression in MC3T3-E1 cells. Furthermore, (-)-epiafzelechin decreased the cell viability of osteoclast precursor cells (P<0.05). It also decreased the number of tartrate resistance acid phosphatase (TRAP) positive multinucleated osteoclastic cells and suppressed the TRAP activity under the induction of receptor activation of nuclear factor kappa-B ligand. These results suggested that (-)-epiafzelechin could promote osteoblasts differentiation and prevent osteoclasts maturation at the effective concentrations between 10nM and 1μM. | en_US |
| dcterms.abstract | (-)-Epiafzelechin was further characterized in animal model. In order to determine the pharmacokinetic (PK) parameters of (-)-epiafzelechin in C57BL/6J mice model, a detection method for plasma (-)-epiafzelechin was established. The (-)-epiafzelechin in plasma samples were extracted from the plasma by liquid/liquid extraction and detected by the liquid chromatography coupled with mass spectrometric detectors. This detection method fulfilled the method validation requirements suggested by US food and drug administration and international conference on harmonization of technical requirements for registration of pharmaceuticals for human use, which could be used to quantify the (-)-epiafzelechin concentration in plasma. The plasma concentration-time profile was used to determine the PK parameters of (-)-epiafzelechin. A single bolus intraperitoneal (i.p.) injection of (-)-epiafzelechin at 10mg/kg could rise the maximum plasma (-)-epiafzelechin concentration to 5.8mg/ml at 15 minutes after administration. From this profile, the elimination half-life of (-)-epiafzelechin was found to be 116 minutes. These results suggested that the plasma (-)-epiafzelechin level could be maintained at above 10nM for 10 hours after an i.p. injection of 10mg/kg (-)-epiafzelechin. In summary, flavan-3-ols were found to exert estrogenic-like activities on bone cells. (-)-epiafzelechin was found to be one of the active ingredients in DF that could modulate the bone remodeling process. A bioanalytical method was successfully developed for quantifying the plasma (-)-epiafzelechin concentration. PK study indicated that (-)-epiafzelechin could be absorbed and maintained in mice plasma at the effective dose. | en_US |
| dcterms.extent | xxii, 214 leaves : ill. (some col.) ; 30 cm. | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2013 | en_US |
| dcterms.educationalLevel | All Doctorate | en_US |
| dcterms.educationalLevel | Ph.D. | en_US |
| dcterms.LCSH | Medicine, Chinese. | en_US |
| dcterms.LCSH | Bones -- Diseases | en_US |
| dcterms.LCSH | Hong Kong Polytechnic University -- Dissertations | en_US |
| dcterms.accessRights | open access | en_US |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| b26526864.pdf | For All Users | 3.78 MB | Adobe PDF | View/Open |
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