Diverse Polycyclic Polyprenylated Acylphloroglucinol Congeners with Anti-Nonalcoholic Steatohepatitis Activity from Hypericum forrestii

Abstract

The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A–J (1–10), were isolated from the fruits of Hypericum forrestii, together with 30 biogenetic congeners of known structures. The structures of hyperforcinols A–J were determined by HRESIMS and 1D/2D NMR spectroscopic analysis, and their absolute configurations were determined by a combination of the electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis. A selection of 25 isolates, possessing seven types of carbon skeletons, were assessed for their in vitro effects against nonalcoholic steatohepatitis (NASH) using a free fatty acid-induced L02 cell model. Compounds 20 and 40 significantly decreased intracellular lipid accumulation. QRT-PCR analyses revealed that compounds 20 and 40 regulate the expression of lipid metabolism-related genes, including CD36, FASN, PPARα, and ACOX1.