Natural ligands for nuclear receptors: biology and potential therapeutic applications

Nuclear receptors are key regulators of various processes including reproduction, development, and metabolism of xeno- and endobiotics. Research in the last two decades has focused to the development of novel drugs specifically targeting nuclear receptors for the treatment of a variety of diseases, such as cancer, diabetes, dyslipidemia, fatty liver disease, drug hepatotoxicity and cholestasis. The search for novel NRs agonists and antagonists with enhanced selectivity prompted the exploration of the extraordinary chemical diversity associated to natural products. In recent years a number of natural products were disclosed as ligands of NRs and proved to have remarkable affinity and in some cases peculiar mode of action. In this review the natural ligands of the subfamily NR1, NR2, and NR3 will be described with an emphasis to their mechanisms of action and pharmacological profiles.