Enzymatic transformation products of phloretin as potent anti-adipogenic compounds.

Enzymatic structure modification of the representative chalcone phloretin (1) with polyphenol oxidase from Agaricus bisporus origin produced two new biphenyl-type phloreoxin (2) and phloreoxinone (3), and a previously undescribed (2R)-5,7,3",5"-tetrahydroxyflavanone (4). The structure of these new oxidized products 2‒4 elucidated by interpreting the spectroscopic data (NMR and FABMS) containing the absolute stereochemistry established by analysis of the circular dichroism (CD) spectrum. Compared to the original phloretin, the new products (2) and (3) showed highly improved anti-adipogenic potencies both toward pancreatic lipase and accumulation of 3T3-L1 cells. Aslo, phloreoxin (2) effectively inhibited the expression of C/EBPβ, PPARγ, and aP2 at the mRNA level in the 3T3 adipocytes. Thus, phloreoxin (2), containing a biphenyl moiety catalyzed by A. bisporus polyphenol oxidase, have the potential to influence the anti-adipogenic capacity.