Identification of a new metabolite of astilbin, 3'-O-methylastilbin, and its immunosuppressive activity against contact dermatitis

Clin Chem. 2007 Mar;53(3):465-71. doi: 10.1373/clinchem.2006.077297. Epub 2007 Feb 1.

Abstract

Background: Astilbin is a flavonoid isolated from the rhizome of Smilax glabra. In a previous study, we revealed its unique immunosuppressive activity, a selective inhibition against activated T lymphocytes. This characteristic of astilbin is beneficial for the treatment of human immune diseases.

Methods: We incubated astilbin with rat liver microsomal/cytosolic fractions and isolated the metabolite of astilbin, which was fully characterized by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. We administered astilbin orally via a gastric tube to rats at 0.22 mmol/kg and collected whole blood samples after 30 min and urine samples after 0 to 12 h. We applied HPLC and liquid chromatography/MS to measure the metabolite in the samples, and we assayed cytokine expression by reverse-transcription PCR.

Results: After incubation of astilbin with rat liver microsomal/cytosolic fractions, we detected a new metabolite of astilbin and isolated it from the culture solution. We characterized this metabolite by MS and NMR techniques as 3'-O-methylated astilbin. We detected the metabolite in both blood and urine samples after oral administration of astilbin, and the metabolite inhibited picryl chloride-induced ear swelling in mice and suppressed the expression of tumor necrosis factor-alpha and interferon-gamma, similarly to astilbin.

Conclusion: This is the first identification of 3'-O-methylastilbin as a new flavonoid, as well as an active metabolite of astilbin in vivo, and is helpful for studying the kinetics of astilbin and its clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dermatitis, Allergic Contact / drug therapy*
  • Edema / chemically induced
  • Edema / immunology
  • Female
  • Flavonols / metabolism*
  • Flavonols / pharmacology*
  • Flavonols / therapeutic use
  • Humans
  • Immunosuppressive Agents / metabolism*
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microsomes, Liver / metabolism
  • Picryl Chloride
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • 3'-O-methylastilbin
  • Flavonols
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • astilbin
  • Interferon-gamma
  • Picryl Chloride