The precise etiology and pathogenesis of idiopathic pulmonary fibrosis are not completely understood, and no satisfactory treatment exists. This work aimed to examine the effects of calycosin (CA, an isoflavone compound) on pulmonary fibrosis (PF) and explore the underlying mechanism. In this study, we established a mice model of PF induced by 5 mg/mL bleomycin (BLM), and mice were orally administrated with 7 mg/kg or 14 mg/kg CA once a day for three weeks. In vitro, after pretreated with 80 μM CA, MLE-12 cells were stimulated with 10 ng/mL transforming growth factor-β1 (TGF-β1) for inducing epithelial-mesenchymal transition (EMT). The results showed that CA treatment ameliorated the severity of fibrosis and the lung tissue damage, as well as suppressed the secretion of inflammation factors in a dose-dependent manner of the PF mice model induced by BLM. Subsequently, CA inhibited the BLM-induced PF progression by repressing EMT, evidenced by the reverse of the downregulation of E-cadherin and the upregulation of vimentin, α-SMA, and fibronectin. Moreover, the elevated phosphorylation of AKT and GSK3β induced by BLM (or TGF-β1) was decreased by CA treatment, leading to the rescue of the high expression of β-catenin. CA prevented the translocation of β-catenin from the cytoplasm to the nucleus. The repressed effects of CA on the TGF-β1-induced EMT and the AKT/GSK3β/β-catenin axis, as well as the translocation of β-catenin were all reversed by a AKT activator SC79. Taken together, CA ameliorated PF by the EMT inhibition upon suppressing the AKT/GSK3β/β-catenin signaling pathway.

特发性肺纤维化的确切病因和发病机制尚不完全清楚，也没有令人满意的治疗方法。这项工作旨在检查花萼素（CA，一种异黄酮化合物）对肺纤维化 (PF) 的影响并探索其潜在机制。在本研究中，我们建立了 5 mg/mL 博来霉素 (BLM) 诱导的 PF 小鼠模型，小鼠每天口服 7 mg/kg 或 14 mg/kg CA 一次，持续 3 周。体外, 用 80 μM C​​A 预处理后，用 10 ng/mL 转化生长因子-β1 (TGF-β1) 刺激 MLE-12 细胞诱导上皮-间质转化 (EMT)。结果表明，CA 治疗可改善 BLM 诱导的 PF 小鼠模型的纤维化严重程度和肺组织损伤，并以剂量​​依赖性方式抑制炎症因子的分泌。随后，CA 通过抑制 EMT 来抑制 BLM 诱导的 PF 进展，这可以通过 E-钙粘蛋白的下调和波形蛋白、α-SMA 和纤连蛋白的上调的逆转来证明。此外，CA 处理降低了由 BLM（或 TGF-β1）诱导的 AKT 和 GSK3β 磷酸化升高，从而挽救了 β-连环蛋白的高表达。CA 阻止 β-连环蛋白从细胞质转移到细胞核。CA 对 TGF-β1 诱导的 EMT 和 AKT/GSK3β/β-连环蛋白轴的抑制作用以及 β-连环蛋白的易位均被 AKT 激活剂 SC79 逆转。总之，CA 在抑制 AKT/GSK3β/β-catenin 信号通路后通过 EMT 抑制改善了 PF。