Matrix metalloproteinase-1 inhibitory activities of Morinda citrifolia seed extract and its constituents in UVA-irradiated human dermal fibroblasts

Biol Pharm Bull. 2012;35(2):210-5. doi: 10.1248/bpb.35.210.

Abstract

The objective of this study was to examine whether a 50% ethanolic extract (MCS-ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 μg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3'-bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 μM without cytotoxic effects. Furthermore, 1 (0.3 μM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen-activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 μM) reduced the phosphorylations of p38 and c-Jun-N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down-regulation of MAPKs phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Dioxins / pharmacology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Humans
  • Infant, Newborn
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lignans / pharmacology
  • Male
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Morinda*
  • Plant Extracts / pharmacology*
  • Protease Inhibitors / pharmacology*
  • Quercetin / pharmacology
  • Seeds
  • Triterpenes / pharmacology
  • Ultraviolet Rays
  • Ursolic Acid
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Dioxins
  • Lignans
  • Matrix Metalloproteinase Inhibitors
  • Plant Extracts
  • Protease Inhibitors
  • Triterpenes
  • americanin A
  • Quercetin
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MMP1 protein, human
  • Matrix Metalloproteinase 1