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

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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… Click to show full 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, PPARĪ±, and ACOX1.

Keywords: polyprenylated acylphloroglucinol; nonalcoholic steatohepatitis; diverse polycyclic; hypericum forrestii; polycyclic polyprenylated

Journal Title: Journal of natural products
Year Published: 2021

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