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

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.

Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

“…3D culture and immunofluorescence staining of fibroblasts were performed as previously described with minor modifications [ 53 ]. For 3D culture of fibroblasts, foreskin fibroblasts (8 × 10 5 cells/mL) were trypsinized and resuspended in 2.8 mg/mL collagen I solution (4 mg/mL rat tail Corning ® collagen I:10× DMEM:10× reconstitution buffer [260 mM NaHCO 3 , 200 mM HEPES, and 50 mM NaOH]:2 µg/mL TNC = 7:1:1:1).…”

A Network Pharmacological Approach to Reveal the Pharmacological Targets and Its Associated Biological Mechanisms of Prunetin-5-O-Glucoside against Gastric Cancer

“…Ginsenoside Rh1 (Rh1) inhibited colorectal cancer cell migration and invasion by partial inhibition of MMP1 and MMP3 [ 35 ]. Skullcapflavone II, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to possess anticancer activity in human skin fibroblasts by suppressing MMP1 transcription [ 36 ].…”

Effect of Elaeagnus umbellata (Thunb.) fruit extract on H2O2-induced oxidative and inflammatory responses in normal fibroblast cells

“…As previously mentioned, MMPs are associated with collagen degradation during oxidative stress. Lee, Seo & Lee (2019) found that Skullcapflavone II (a flavonoid derived from the Scutellaria baicalensis root) decreased MMP-1 expression and improved the integrity of type I collagen in foreskin fibroblasts. In recent years, there has been a greater use of natural substances which, instead of reducing MMP expression, increase the expression of their inhibitors (tissue inhibitors of metalloproteinases, TIMPs).…”