Prenylated Flavonoids from Cudrania tricuspidata Suppress Lipopolysaccharide-Induced Neuroinflammatory Activities in BV2 Microglial Cells

Int J Mol Sci. 2016 Feb 19;17(2):255. doi: 10.3390/ijms17020255.

Abstract

In Korea and China, Cudrania tricuspidata Bureau (Moraceae) is an important traditional medicinal plant used to treat lumbago, hemoptysis, and contusions. The C. tricuspidata methanol extract suppressed both production of NO and PGE₂ in BV2 microglial cells. Cudraflavanone D (1), isolated from this extract, remarkably suppressed the protein expression of inducible NO synthase and cyclooxygenase-2, and decreased the levels of NO and PGE₂ in BV2 microglial cells exposed to lipopolysaccharide. Cudraflavanone D (1) also decreased IL-6, TNF-α, IL-12, and IL-1β production, blocked nuclear translocation of NF-κB heterodimers (p50 and p65) by interrupting the degradation and phosphorylation of inhibitor of IκB-α, and inhibited NF-κB binding. In addition, cudraflavanone D (1) suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. This study indicated that cudraflavanone D (1) can be a potential drug candidate for the cure of neuroinflammation.

Keywords: Cudrania tricuspidata; cudraflavanone D; microglia; mitogen-activated protein kinase; neuroinflammation; nuclear factor-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Gene Expression Regulation / drug effects
  • Lipopolysaccharides / adverse effects*
  • Mice
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / metabolism
  • Moraceae / chemistry*
  • Nitric Oxide Synthase / metabolism
  • Prenylation

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drugs, Chinese Herbal
  • Flavonoids
  • Lipopolysaccharides
  • Nitric Oxide Synthase
  • Cyclooxygenase 2