Biological and Chemical Investigation of Panamanian Plants for Potential Utility against Metabolic Syndrome

Metabolic syndrome (MetS) affects approximately 25% of the adult population of the world and represents a public health concern with high socioeconomic impact worldwide. Latin American populations exhibit a high prevalence of MetS, similar or even higher than developed countries. This complex and progressive disorder can develop over many years as a cluster of conditions characterized by a constellation of metabolic abnormalities. Specific guidelines have not yet been established for the treatment of MetS per se. The increased prevalence of MetS has been associated with a greater risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In fact, new anti-diabetic drugs that do not display undesirable side effects, such as hepatotoxicity, edema and weight gain, are in great demand. For these reasons, the overall goal of this study was centered on four molecular targets: peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) which are key regulators of various processes leading to metabolic disorder and inflammation. As a part of inflammatory pathway, activation of NF-κB leads to insulin resistance and by blocking this pathway, insulin resistance and the resultant T2DM can be prevented. In contrast, activators of PPARa and PPARg are effective in lowering blood lipids and sugar and have been considered useful in the treatment of obesity and diabetes. Like the PPARs, LXR suppresses production of inflammatory mediators in a manner reciprocal to its regulation of lipid metabolism. In order to explore natural products working through these specific pathways this dissertation was focused on Panamanian flora as a primary source. A total of 75 plant species belonging to 71 genera and 41 families were screened for their effects on the selected targets trough cellular assays. Due to a lack of literature available on the biological activity towards MetS and lack of the phytochemical characterization, two plants ( Talisia nervosa and Odontadenia puncticulosa) were selected for bioassay-guided fractionation through PPARα and PPARγ activation assay. The current study relied on Panamanian flora as a source of new therapeutic agents directed toward the mitigation of metabolic abnormalities