Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats
Thesis (PhD (Human Physiology))--University of Pretoria, 2025.
Saved in:
| Other Authors: | |
|---|---|
| Format: | Thesis |
| Language: | English |
| Published: |
University of Pretoria
2025
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613528753438720 |
|---|---|
| access_status_str | Open Access |
| author2 | Nyakudya, Trevor Tapiwa |
| author_browse | Nyakudya, Trevor Tapiwa |
| author_facet | Nyakudya, Trevor Tapiwa |
| collection | Thesis |
| dc_rights_str_mv | © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD (Human Physiology))--University of Pretoria, 2025. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/101288 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:37:35.225Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/101288 The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats Nyakudya, Trevor Tapiwa u21782386@tuks.co.za Kasonga, Abe E. Joubert, Annie M. De Vos, Brunhildé UCTD Sustainable Development Goals (SDGs) Zingerone Osteoporosis Phytonutrients Alcohol Bone morphometry Thesis (PhD (Human Physiology))--University of Pretoria, 2025. Background: Bone health is fundamental for overall human health, providing structural support, calcium homeostasis, organ protection, and facilitating muscle function. Disruptions in bone metabolism, caused by factors such as aging, hormonal imbalances, or lifestyle factors, can lead to metabolic bone diseases such as osteoporosis, characterised by reduced bone mass and increased risk of fracture. Phytochemicals have shown potential in managing bone metabolic disorders. Among these, zingerone a key compound isolated from cooked ginger (Zingiber officinale), has gained attention for its anti-inflammatory, antioxidant, and anticancer properties. Structurally, the phenolic and ketone groups of zingerone enable free radical scavenging, cytokine inhibition, and modulation of signalling pathways such as mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB). These findings suggest that zingerone may support bone health by promoting osteoblast differentiation and inhibiting osteoclastogenesis, thereby preserving bone integrity. Aim: The study aimed to investigate the osteogenic potential of zingerone in vitro using osteoblast- (SAOS-2) and osteoclast-derived (RAW264.7) cells. This study also investigated the effects of neonatal zingerone administration on bone health in a rodent model of alcohol-induced bone dysfunction, providing insights into its potential benefits in maintaining bone health. Methods: The in vitro objectives were to evaluate the effects of zingerone on bone cell activity and function. Cytotoxic concentrations of zingerone were evaluated via resazurin assay, while osteoblast mineralisation was analysed using Alizarin Red S staining. Osteoblast activity was assessed through alkaline phosphatase (ALP) activity and gene expression of early (Runt-related transcription factor 2 (Runx2), ALP and late (osteocalcin) markers of osteoblastogenesis using quantitative polymerase chain reaction (q-PCR). Osteoclastogenesis was assessed in osteoclast-derived RAW264.7 cells using tartrate-resistant acid phosphatase (TRAP) staining, and osteoclast activity was evaluated using colorimetric TRAP activity assays. Additionally, osteoclast-specific protein expression was assessed involving MAPK and NF-κB signalling pathways via western blotting. A pre-existing in vivo animal model was used to evaluate the potential beneficial effects of zingerone as a dietary supplement in mitigating neonatal and adolescent alcohol-induced bone dysfunction. Blood plasma markers of bone function were assessed using bone-specific alkaline phosphatase, osteocalcin, and procollagen type 1 N-terminal propeptide (P1NP), through enzyme-linked immunosorbent assays (ELISA). Bone morphometry of the tibia (n=7/group) was determined by measuring the bone mass-to-length ratio, and internal bone morphometry was analysed using micro-computed tomography (micro-CT). Results: In vitro findings revealed that zingerone at 200 µM enhanced bone cell activity by reducing osteoclast numbers and TRAP activity by 22% in RAW264.7 cells while promoting early stages of osteoblast differentiation by upregulating genes such as Runx2 and ALP by 50–80% in SAOS-2 cells (p<0.05). Complementary in vivo findings demonstrated that neonatal administration of zingerone at a dose of 40 mg/kg body mass in conjunction with adolescent alcohol exposure was associated with potential impaired bone health. These included decreased plasma P1NP, reduced tibial mass, and thinner, more widely spaced trabeculae. In contrast, rats exposed to neonatal and adolescent alcohol exhibited a 49% increase in cortical thickness and a 120% elevation in P1NP levels (vs M+W, p<0.05). However, the neonatal combination of zingerone with alcohol (1 g/kg body mass) demonstrates potential for further investigation as a prospective therapeutic intervention. Conclusion: Zingerone demonstrates moderate potentials in modulating bone remodelling, however its effects on bone mass and quality remains inadequately characterised. Additional research is required to fully elucidate its underlying mechanisms and to evaluate its efficacy with established antiresorptive medications. National Research Foundation (NRF) of South Africa, Grant Number: 121828 Physiology PhD (Human Physiology) Unrestricted Faculty of Health Sciences SDG-03: Good health and well-being 2025-03-02T23:22:55Z 2025-03-02T23:22:55Z 2025-04 2025-02 Thesis * A2025 http://hdl.handle.net/2263/101288 DOI: https://doi.org/10.25403/UPresearchdata.28524380.v1 https://figshare.com/s/21d4df59c40840545613 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Sustainable Development Goals (SDGs) Zingerone Osteoporosis Phytonutrients Alcohol Bone morphometry The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats |
| title | The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats |
| title_full | The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats |
| title_fullStr | The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats |
| title_full_unstemmed | The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats |
| title_short | The effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in Sprague Dawley rats |
| title_sort | effects of zingerone on differentiation and signalling pathways in bone cell lines and bone health parameters in sprague dawley rats |
| topic | UCTD Sustainable Development Goals (SDGs) Zingerone Osteoporosis Phytonutrients Alcohol Bone morphometry |
| url | http://hdl.handle.net/2263/101288 https://figshare.com/s/21d4df59c40840545613 |