- Title
- Comprehensive characterization of the antidiabetic potential of selected plants and macrofungi from Africa using an in vitro target-directed screening platform and cellomics
- Creator
- Pringle, Nadine Alex
- Subject
- Hypoglycemic agents
- Date Issued
- 2020
- Date
- 2020
- Type
- Thesis
- Type
- Doctoral
- Type
- PhD
- Identifier
- http://hdl.handle.net/10948/46750
- Identifier
- vital:39653
- Description
- Several synthetic antidiabetic drugs have been developed to date, however, most are accompanied by adverse side-effects while remaining expensive and largely inaccessible to the vast majority of those who need it. To provide enough scientific evidence to support the inclusion of more affordable African antidiabetic medicinal plants and macrofungi into healthcare programs, this study sought out to develop a comprehensive in vitro antidiabetic target-directed screening platform incorporating high content screening and analysis/ cellomics. To test the success of this model, the potential antidiabetic mechanisms of five plants (Aspalathus linearis, Brachylaena discolor, Carpobrotus deliciosus, Sutherlandia frutescens and Tarchonanthus camphoratus) and two macrofungal species (Ganoderma lucidum and Hericium erinaceus) were explored. The screening model consisted of approximately 22 assays exploring the antidiabetic effects of selected aqueous and ethanolic extracts in five well-characterised antidiabetic targets: the intestine, liver, skeletal muscle, adipose tissue/ obesity and pancreatic β-cells. These targets were further categorised and scored under three mechanistic classes/ therapeutic targets (postprandial hyperglycaemia; insulin resistance and inflammation; pancreatic β-cell function) to elucidate their potential mechanisms of action and select appropriate animal models for future studies. Almost any normal or diabetic rodent model would be suitable to explore the antidiabetic potential of extracts such as A. linearis, B. discolor ethanol, C. deliciosus ethanol or T. camphoratus which obtained high cumulative scores under postprandial hyperglycaemia while high fat diet and genetic models of obesity appear more suited towards extracts such as H. erinaceus aqueous that obtained their highest cumulative score under insulin resistance. In general, a combination of rodent models ranging from non-obese models to models of obesity and β-cell destruction presenting symptoms from all three mechanistic classes should be considered due to the pleiotropic nature of the tested extracts, however, establishing appropriate experimental designs is crucial. To demonstrate the versatility of the screening platform and emphasise the importance of in vitro screening pertaining to diabetic complications, a more detailed biochemical investigation into the potential therapeutic benefits of A. linearis in the treatment of diabetic wounds was conducted. Several properties supporting the therapeutic potential of rooibos were highlighted with the green and fermented extracts presenting distinctly different characteristics. The pro-inflammatory nature of fermented rooibos may have therapeutic value for wounds characterised with a delayed initial inflammatory phase, such as early diabetic wounds while the green extract appears more suited to wounds burdened with excessive inflammation as it attenuated COX-2 levels and effectively protected fibroblasts against oxidative stress. To date, this appears to be the most comprehensive antidiabetic screening platform in existence and consequently provides the only feasible solution that will enable natural product antidiabetic research to progress to the point where natural products can be commercialised and incorporated into meaningful healthcare programs. Future research should be focussed towards further expanding this model by incorporating additional targets, more sophisticated cell culturing techniques, multiplexed high content screening assays and carrying out combination treatments that explore the antidiabetic effects of two or more crude extracts to establish whether they are capable of acting in a synergistic manner.
- Format
- xvii, 239 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
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NMU School of Medicinal Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Pringle, N 212418181 Thesis April 2020.pdf | 7 MB | Adobe Acrobat PDF | View Details Download |