BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible disease characterized by excessive fibroblast to myofibroblast differentiation with limited therapeutic options. Curdione, a sesquiterpene compound extracted from the essential oil of Curcuma aromatica Salisb, has anti-inflammatory and anti-tumor effects. However, the role of curdione in IPF is still unclear. METHODS The effects of curdione were evaluated in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. C57BL/6 mice were treated with BLM on day 0 by intratracheal injection and intraperitoneal administered curdione or vehicle. In vitro study, expression of fibrotic protein was examined and the transforming growth factor (TGF)-β-related signaling was evaluated in human pulmonary fibroblasts (HPFs) treated with curdione following TGF-β1 stimulation. RESULTS Histological and immunofluorescent examination showed that curdione alleviated BLM-induced lung injury and fibrosis. Specifically, curdione significantly attenuated fibroblast to myofibroblast differentiation in the lung in BLM induced mice. Furthermore, curdione also decreased TGF-β1 induced fibroblast to myofibroblast differentiation in vitro, as evidenced by low expression of α-SMA, collagen 1 and fibronectin in a dose dependent manner. Mechanistically, curdione suppressed the phosphorylation of Smad3 following TGF-β1 treatment, thereby inhibiting fibroblast differentiation. CONCLUSIONS Overall, curdione exerted therapeutic effects against pulmonary fibrosis via attenuating fibroblast to myofibroblast differentiation. As curdione had been shown to be safe and well-tolerated in BLM-induced mouse model, curdione might be useful for developing novel therapeutics for IPF.

中文翻译：

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Curdione 通过抑制 TGF-β 诱导的成纤维细胞向肌成纤维细胞分化来改善博来霉素诱导的肺纤维化。

背景特发性肺纤维化（IPF）是一种进行性和不可逆的疾病，其特征是成纤维细胞过度分化为肌成纤维细胞，治疗选择有限。姜二酮是一种从姜黄精油中提取的倍半萜类化合物，具有抗炎和抗肿瘤作用。然而，curdione 在 IPF 中的作用仍不清楚。方法 在博来霉素 (BLM) 诱导的肺纤维化小鼠模型中评估 curdione 的作用。C57BL/6 小鼠在第 0 天通过气管内注射和腹膜内给予 curdione 或载体用 BLM 治疗。在体外研究中，检查了纤维化蛋白的表达，并在 TGF-β1 刺激后用 curdione 处理的人肺成纤维细胞 (HPF) 中评估了转化生长因子 (TGF)-β 相关信号。结果组织学和免疫荧光检查显示，curdione 减轻了 BLM 引起的肺损伤和纤维化。具体而言，在 BLM 诱导的小鼠中，curdione 显着减弱了肺中成纤维细胞向肌成纤维细胞的分化。此外，curdione 还在体外降低了 TGF-β1 诱导的成纤维细胞向肌成纤维细胞的分化，α-SMA、胶原蛋白 1 和纤连蛋白的低表达以剂量依赖性方式证明了这一点。从机制上讲，curdione 在 TGF-β1 处理后抑制 Smad3 的磷酸化，从而抑制成纤维细胞分化。结论 总体而言，curdione 通过减弱成纤维细胞向肌成纤维细胞的分化发挥抗肺纤维化的治疗作用。由于 curdione 在 BLM 诱导的小鼠模型中被证明是安全且耐受性良好的，