Scutellarin-dependent inhibition of collagen biosynthesis in cultured fibroblasts

The effects of the flavonoid compound scutellarin (SCUT) on collagen biosynthesis, prolidase activity, expression of β₁ integrin, insulin-like growth factor-I (IGF-I) receptor and the transcription factor NF-κB were evaluated in human dermal fibroblasts. Confluent fibroblasts were treated with micromolar concentrations (10-30 µM) of SCUT for 24 h. It was found that a SCUT-dependent decrease in collagen biosynthesis was accompanied by an increase in prolidase activity. Since the IGF-I receptor (IGF-IR) is the most potent regulator of both collagen biosynthesis and prolidase activity, and prolidase is regulated by β₁ integrin signalling, the effect of SCUT on IGF-IR and β₁ integrin receptor expressions were evaluated. It was found that the exposure of the cells to SCUT contributed to an increase in IGF-IR and β₁ integrin receptor expressions. This was accompanied by an increase in expression of NF-κB, the known inhibitor of collagen gene expression. These data suggest that the SCUT-dependent decrease of collagen biosynthesis in cultured human skin fibroblasts results from activation of NF-κB, which is responsible for the down-regulation of collagen gene expression.