Prenylated Flavonoids from the Roots and Rhizomes of Sophora tonkinensis and Their Effects on the Expression of Inflammatory Mediators and Proprotein Convertase Subtilisin/Kexin Type 9

J Nat Prod. 2019 Feb 22;82(2):309-317. doi: 10.1021/acs.jnatprod.8b00748. Epub 2019 Jan 30.

Abstract

Seven new prenylated flavonoids (1-7) and one new prenylated phenylpropiophenone (8) were isolated from roots and rhizomes of Sophora tonkinensis, along with nine known compounds (9-17). The structures 1-8 were elucidated by spectroscopic data analysis and comparison with reported values. Compounds 8 and 12 (7-methoxyebenosin) showed inhibitory activities against nitric oxide production in lipopolysaccharide-induced RAW264.7 cells, with IC50 values of 8.1 and 6.2 μM, respectively. They also significantly lowered expression of CSF2, TNF, and IL-1β. Lonchocarpol A (10) and erybraedin D (16) at concentrations of 20 μM downregulated proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA expression in HepG2 cells. Moreover, erybraedin D (16) inhibited PCSK9 protein synthesis (IC50 7.8 μM), while simultaneously activating AMP-activated protein kinase and acetyl-CoA carboxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Flavonoids / isolation & purification*
  • Flavonoids / pharmacology
  • Hep G2 Cells
  • Humans
  • Inflammation Mediators / analysis
  • Inflammation Mediators / antagonists & inhibitors*
  • Mice
  • Nitric Oxide / antagonists & inhibitors
  • PCSK9 Inhibitors*
  • Plant Roots / chemistry
  • Prenylation
  • Proprotein Convertase 9 / genetics
  • RAW 264.7 Cells
  • Sophora / chemistry*

Substances

  • Flavonoids
  • Inflammation Mediators
  • PCSK9 Inhibitors
  • Nitric Oxide
  • Proprotein Convertase 9