| According to the latest facts and figures from the Centers for Disease Control, the prevalence of obesity and Type-2 Diabetes Mellitus (T2DM) across all demographics is escalating worldwide. Among the range of drugs used to treat diabetes there is an interest in treatment options that are derived from more traditional methods, outside of the customarily synthetic and pharmaceutically sourced treatment options. Amid treatment alternatives that are more traditional in origin are a category of compounds called natural products. The natural products of interest are either plant based extracts or specific organic compounds extracted from the natural product. Over the last decade, plant based natural products have been increasingly shown to provide an alternative and supplementary course of treatment for diabetic patients suffering from systemic inflammation and insulin resistance in model systems of metabolic disease. However, information for many natural products is limited to small studies with mixed outcomes and information on human models systems remains limited in scope. In this thesis the most potent therapeutic natural products were evaluated by conducting a thorough literature review and subsequently studying the most promising candidates by characterizing their metabolic effects on human adipocytes. In order to identify the most potent plant based natural products we will use cultured human adipocytes as a model system. Free-fatty acids (FFA) and cytokines including Tumor Necrosis Factor-alpha (TNF-&agr;), have been demonstrated to impair fat metabolism and reduce insulin signaling. Therefore, we will study the protective effect of prominent and potentially beneficial natural compounds, based on comprehensive literature reviews, to assess their effect on FFA metabolism using glycerol release as a measure of lipolysis, cytokine induced lipolysis as a measure of natural product protection against inflammation, and impaired AKT-phosphorylation as a measure of insulin signaling function. Observations gathered concluded that the application of bitter melon, fenugreek, and ginseng plant extracts reduced lipolysis in a dose dependent manner, limited the effects of TNF-&agr; induced lipolysis, and fenugreek and ginseng displayed pro-apoptotic cellular programs. |
