Secoiridoid Glycosides from the Twigs of Ligustrum obtusifolium Possess Anti-inflammatory and Neuroprotective Effects

Chem Pharm Bull (Tokyo). 2018;66(1):78-83. doi: 10.1248/cpb.c17-00720.

Abstract

Two new secoiridoid glycosides, obtusifolisides A and B (1, 2), together with 7 known secoiridoid glycosides (3-9) were isolated from the twigs of Ligustrum obtusifolium. The chemical structures of new compounds were determined by a spectroscopic data analysis, including one and two dimensional (1D-, 2D)-NMR, High resolution-MS, and experiments involving chemical reactions. The isolated secoiridoid glycosides were evaluated for their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. Compounds 2, 5, 6, 8, and 9 significantly reduced the production of nitric oxide (NO), with IC50 values of 5.45, 11.17, 14.62, 15.45, and 14.96 µM, respectively. None of the compounds were toxic to the cells. Additionally, we evaluated the neuroprotective effects of compounds 1-9 on nerve growth factor (NGF) induction in a C6 rat glioma cell line. Compounds 2 and 6 upregulated NGF secretion to 155.56±7.16%, and 139.35±11.65%, respectively, without significant cell toxicity.

Keywords: Ligustrum obtusifolium; anti-inflammation; nerve growth factor (NGF) regulation; secoiridoid glycoside.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Glioma / drug therapy
  • Glioma / metabolism
  • Iridoid Glycosides / chemistry
  • Iridoid Glycosides / isolation & purification
  • Iridoid Glycosides / pharmacology*
  • Ligustrum / chemistry*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism
  • Molecular Conformation
  • Nerve Growth Factors / antagonists & inhibitors
  • Nerve Growth Factors / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Plant Stems / chemistry*
  • Rats
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Iridoid Glycosides
  • Lipopolysaccharides
  • Nerve Growth Factors
  • Neuroprotective Agents
  • Nitric Oxide