The important pathway toward liver fibrosis is the TGF-β1-induced activation of hepatic stellate cells (HSCs). To discover chemicals to inhibit liver fibrosis, we screened 3000 chemicals using cell array system where human HSCs line LX2 cells are activated with TGF-β1. We discovered 3,7-dimethoxyflavone (3,7-DMF) as a chemical to inhibit TGF-β1-induced activation of HSCs.

In the thioacetamide (TAA)-induced mouse liver fibrosis model, 3,7-DMF treatment via intraperitoneal or oral administration prevented liver fibrosis as well as reversed the established fibrosis in the separate experiments. It also reduced liver enzyme elevation, suggesting protective effect on hepatocytes because it has antioxidant effect. Treatment with 3,7-DMF induced antioxidant genes, quenches ROS away, and improved the hepatocyte condition that was impaired by H₂O₂ as reflected by restoration of HNF-4α and albumin. In the TAA-mouse liver injury model also, TAA significantly increased ROS in the liver which led to decrease of albumin and nuclear expression of HNF-4α, increase of TGF-β1 and hepatocytes death, accumulation of lipid, and extra-nuclear localization of HMGB1. Treatment of 3,7-DMF normalized all these pathologic findings and prevented or resolved liver fibrosis.

In conclusion, we discovered 3,7-DMF that inhibits liver fibrosis based on dual actions; antioxidant and inhibitor of TGF-β1-induced activation of HSCs.

肝纤维化的重要途径是 TGF-β1 诱导的肝星状细胞 (HSC) 激活。为了发现抑制肝纤维化的化学物质，我们使用细胞阵列系统筛选了 3000 种化学物质，其中人类 HSCs 系 LX2 细胞被 TGF-β1 激活。我们发现 3,7-二甲氧基黄酮 (3,7-DMF) 作为一种化学物质可抑制 TGF-β1 诱导的 HSC 活化。

在硫代乙酰胺 (TAA) 诱导的小鼠肝纤维化模型中，通过腹膜内或口服给药的 3,7-DMF 治疗可预防肝纤维化，并在单独的实验中逆转已建立的纤维化。它还降低了肝酶升高，表明对肝细胞有保护作用，因为它具有抗氧化作用。_{用 3,7-DMF 处理诱导抗氧化基因，淬灭 ROS，并改善被 H 2} O ₂损害的肝细胞状况正如 HNF-4α 和白蛋白的恢复所反映的那样。在 TAA 小鼠肝损伤模型中，TAA 显着增加肝脏中的 ROS，导致白蛋白减少和 HNF-4α 的核表达，TGF-β1 增加和肝细胞死亡，脂质积累和核外定位HMGB1。3,7-DMF 的治疗使所有这些病理结果正常化，并预防或解决了肝纤维化。

总之，我们发现了基于双重作用抑制肝纤维化的3,7-DMF；TGF-β1 诱导的 HSC 活化的抗氧化剂和抑制剂。