Skullcapflavone II Inhibits Degradation of Type I Collagen by Suppressing MMP-1 Transcription in Human Skin Fibroblasts.

Young Hun Lee,Seung-Taek Lee,Eun Kyoung Seo

doi:10.3390/ijms20112734

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.

Highlights

Skullcapflavone II, a naturally occurring flavonoid compound with a polyphenolic structure known as neobaicalein, is derived from the roots of Scutellaria baicalensis, S. litwinowii, and S. pinnatifida [1,2,3]
Because skullcapflavone II exhibits anti-inflammatory activity, we investigated the effect of skullcapflavone II on the expression of matrix metalloproteinase-1 (MMP-1) and the integrity of type I collagen in fibroblasts
We investigated the effect of skullcapflavone II (Figure S1) on the secretion of Matrix metalloproteinases (MMPs)-1 and type I collagen in primary human foreskin fibroblasts and primary human buttock dermal fibroblasts

Summary

Introduction

Skullcapflavone II, a naturally occurring flavonoid compound with a polyphenolic structure known as neobaicalein, is derived from the roots of Scutellaria baicalensis, S. litwinowii, and S. pinnatifida [1,2,3]. Biological functions attributed to skullcapflavone II include reducing inflammation, inhibiting osteoclastogenesis, decreasing cell growth, inducing apoptosis, and down-regulating cholesterol [2,4,5,6,7]. Skullcapflavone II inhibits ovalbumin-induced airway inflammation via a decrease in transforming growth factor-β1 expression and subsequent decrease in SMAD2/3 activation [4]. Skullcapflavone II inhibits osteoclastogenesis with reduced activation of mitogen-activated protein kinases (MAPKs), Src, and cyclic adenosine monophosphate (cAMP) response element binding protein, and attenuates the survival and bone resorption function of osteoclasts via down-regulation of integrin signaling [5]. Skullcapflavone II reportedly inhibits the mRNA expression of proprotein convertase subtilisin/kexin type 9, which prevents the recycling of endocytosed low-density-lipoprotein receptors (LDLRs) to the cell surface, thereby increasing cell-surface LDLR levels and lowering plasma cholesterol levels [7]

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