Medicinal Properties of Mangiferin, Structural Features, Derivative Synthesis, Pharmacokinetics and Biological Activities

The identification of biologically active and potentially therapeutically useful pharmacophores from natural products has been a long-term focus in the pharmaceutical industry. The recent emergence of a worldwide obesity and Type II diabetes epidemic has increased focus upon small molecules that can modulate energy metabolism, insulin sensitivity and fat biology. Interesting preliminary work done on mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera indica L., portends potential for this pharmacophore as a novel parent compound for treating metabolic disorders. MGF is comprised of a C-glucosylated xanthone. Owing to the xanthone chemical structure, MGF has a redox active aromatic system and has antioxidant properties. MGF exerts varied and impressive metabolic effects in animals, improving metabolic disorders. For example we have discovered that MGF is a novel activator of the mammalian pyruvate dehydrogenase complex, leading to enhancement of carbohydrate utilization in oxidative metabolism, and leading to increased insulin sensitivity in animal models of obesity and insulin resistance. In addition, recent unbiased proteomics studies revealed that MGF upregulates proteins pivotal for mitochondrial bioenergetics and downregulates proteins controlling de novo lipogenesis in liver, helping to explain protective effects of MGF in prevention of liver steatosis. Several chemical studies have achieved synthesis of MGF, suggesting possible synthetic strategies to alter its chemical structure for development of structure-activity relationship (SAR) information. Ultimately, chemical derivatization studies could lead to the eventual development of novel therapeutics based upon the parent pharmacophore structure. Here we provide comprehensive review on chemical features of MGF, synthesis of its derivatives, its pharmacokinetics and biological activities.