Exp Dermatol. 2013 Jun;22(6):428-30. doi: 10.1111/exd.12157.
We investigated the reported antiphotoaging effects of the major anthocyanidin delphidin and sought to identify its specific molecular target during UVB-induced MMP-1 expression. Delphinidin treatment significantly inhibited UVB-induced MMP-1 expression in primary cultured human dermal fibroblasts (HDF), an effect associated with the suppression of MKK4-JNK1/2, MKK3/6-p38 and MEK-ERK1/2 phosphorylation. Further investigation revealed that delphinidin significantly inhibited UVB-induced ROS production and NOX activity. Interestingly, the inhibitory effect of delphinidin on UVB-induced NOX activity was stronger than that of apocynin, a pharmaceutical NOX inhibitor. Fractioned cell analysis results using a Western blot assay showed that this effect occurred through the inhibition of UVB-induced P47(phox) (a NOX subunit) translocation from the cytosol to the membrane. Pull down assays demonstrated that delphinidin binds directly to P47(phox) in vitro. Collectively, our results suggest that delphinidin targets NOX, resulting in the suppression of UVB-induced MMP-1 expression in human dermal fibroblasts.
我们研究了主要花色苷矢车菊素素报告的抗光老化作用，并试图确定其在 UVB 诱导的 MMP-1 表达过程中的特定分子靶标。矢车菊素素处理显著抑制了原代培养的人真皮成纤维细胞（HDF）中 UVB 诱导的 MMP-1 表达，这种作用与抑制 MKK4-JNK1/2、MKK3/6-p38 和 MEK-ERK1/2 磷酸化有关。进一步的研究表明，矢车菊素素显著抑制了 UVB 诱导的 ROS 产生和 NOX 活性。有趣的是，矢车菊素素对 UVB 诱导的 NOX 活性的抑制作用强于药物 NOX 抑制剂 apocynin。使用 Western blot 分析进行的细胞分馏分析结果表明，这种作用是通过抑制 UVB 诱导的 P47(phox)（一种 NOX 亚基）从细胞质向膜的易位而发生的。下拉测定表明，矢车菊素素在体外直接结合 P47(phox)。总的来说，我们的结果表明，矢车菊素素靶向 NOX，从而抑制了人真皮成纤维细胞中 UVB 诱导的 MMP-1 表达。
