Skin fibrosis is one of the major features of scleroderma. WNT/β-catenin signaling is associated with the progression of skin fibrosis. In this study, we aimed to determine the effect of icaritin (IT), a natural compound, on scleroderma-related skin fibrosis and its mechanisms. We found that IT could reduce the expression of COL1A1, COL1A2, COL3A1, CTGF, and α-SMA in human foreskin fibroblasts (HFF-1 cells), scleroderma skin fibroblasts (SSF cells), and TGF-β-induced HFF-1 cells. Wnt/β-catenin signaling was shown to be suppressed by IT. Additionally, IT activated AMPK signaling in HFF-1 cells. In conclusion, IT has an anti-skin fibrotic effect through activation of AMPK signaling and inhibition of WNT/β-catenin signaling. Our findings indicate the potential role of IT in the treatment of scleroderma and provide novel insight for the selection of drug therapy for scleroderma.

皮肤纤维化是硬皮病的主要特征之一。WNT/β-连环蛋白信号与皮肤纤维化的进展有关。在这项研究中，我们旨在确定一种天然化合物淫羊藿苷 (IT) 对硬皮病相关皮肤纤维化的影响及其机制。我们发现 IT 可以降低人包皮成纤维细胞（HFF-1 细胞）、硬皮病皮肤成纤维细胞（SSF 细胞）和 TGF-β 诱导的 HFF-1 细胞中 COL1A1、COL1A2、COL3A1、CTGF 和 α-SMA 的表达. Wnt/β-连环蛋白信号显示被 IT 抑制。此外，IT 激活了 HFF-1 细胞中的 AMPK 信号传导。总之，IT 通过激活 AMPK 信号传导和抑制 WNT/β-catenin 信号传导具有抗皮肤纤维化作用。