Skullcapflavone II Inhibits Degradation of Type I Collagen by Suppressing MMP-1 Transcription in Human Skin Fibroblasts
- 주제(키워드) extracellular matrix , fibroblast , inflammation , MMP-1 , skullcapflavone II , type I collagen
- 주제(기타) Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
- 설명문(일반) [Lee, Young Hun; Lee, Seung-Taek] Yonsei Univ, Dept Biochem, Coll Life Sci & Biotechnol, Seoul 03722, South Korea; [Seo, Eun Kyoung] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03790, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published, Green Submitted
- 발행기관 MDPI
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159857
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/ijms20112734
- PubMed https://pubmed.ncbi.nlm.nih.gov/31167359
초록/요약
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)--induced nuclear factor kappa light chain enhancer of activated B cells (NF-B) activation and subsequent MMP-1 expression. In three-dimensional culture of fibroblasts, skullcapflavone II down-regulated TNF--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.
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