Skullcapflavone II inhibits degradation of type I collagen by suppressing MMP-1 transcription in human skin fibroblasts

Young Hun Lee, Eun Kyoung Seo, Seung Taek Lee

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12 Scopus citations

Abstract

Skullcapflavone II is a flavonoid derived from the root of Scutellaria baicalensis, a herbal medicine used for anti-inflammatory and anti-cancer therapies. We analyzed the effect of skullcapflavone II on the expression of matrix metalloproteinase-1 (MMP-1) and integrity of type I collagen in foreskin fibroblasts. Skullcapflavone II did not affect the secretion of type I collagen but reduced the secretion of MMP-1 in a dose- and time-dependent manner. Real-time reverse transcription-PCR and reporter gene assays showed that skullcapflavone II reduced MMP-1 expression at the transcriptional level. Skullcapflavone II inhibited the serum-induced activation of the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways required for MMP-1 transactivation. Skullcapflavone II also reduced tumor necrosis factor (TNF)-α-induced nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activation and subsequent MMP-1 expression. In three-dimensional culture of fibroblasts, skullcapflavone II down-regulated TNF-α-induced MMP-1 secretion and reduced breakdown of type I collagen. These results indicate that skullcapflavone II is a novel biomolecule that down-regulates MMP-1 expression in foreskin fibroblasts and therefore could be useful in therapies for maintaining the integrity of extracellular matrix.

Original languageEnglish
Article number2734
JournalInternational Journal of Molecular Sciences
Volume20
Issue number11
DOIs
StatePublished - 1 Jun 2019

Keywords

  • Extracellular matrix
  • Fibroblast
  • Inflammation
  • MMP-1
  • Skullcapflavone II
  • Type I collagen

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