Melanin: dietary mucosal immune modulator from Echinacea and other botanical supplements.

The agents responsible for the therapeutic effects of many botanical supplements have not been established in spite of their popularity. Here we show that melanin is a previously unrecognized immunostimulatory compound that is a major component of botanicals traditionally used to enhance immune function. While melanin is present in commonly consumed vegetables, its specific activity is several orders of magnitude less than melanin extracted from these botanicals. The major reason that this agent has eluded detection is its solvent-specific requirement for extraction/solubility. Melanin activates NF-kappa B in monocytes in vitro through a toll-like receptor 2-dependent process. Ingestion of melanin by mice for four days increases production ex vivo of interferon-gamma by spleen cells and IgA and interleukin-6 by Peyer's patch cells. The identification of this new class of mucosal immune stimulants will allow further characterization of botanical products and advances our understanding of the basis for their traditional use.