Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Wuhan Clinical Medical Research Center for Chronic Airway Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
Department of Respiratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Lu, Shanghai, 201999, China.
Respir Res. 2020 Feb 19;21(1):58. doi: 10.1186/s12931-020-1300-y.
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.
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.
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.
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.
特发性肺纤维化（IPF）是一种进行性和不可逆转的疾病，其特征是成纤维细胞向肌成纤维细胞的分化过度，治疗选择有限。莪术二酮是一种从莪术油中提取的倍半萜化合物，具有抗炎和抗肿瘤作用。然而，莪术二酮在 IPF 中的作用尚不清楚。
在博来霉素（BLM）诱导的肺纤维化小鼠模型中评估莪术二酮的作用。C57BL/6 小鼠通过气管内注射和腹腔内给予莪术二酮或载体在第 0 天用 BLM 处理。在体外研究中，在 TGF-β1 刺激后，用莪术二酮处理人肺成纤维细胞（HPFs），检测纤维化蛋白的表达和 TGF-β 相关信号转导。
组织学和免疫荧光检查表明，莪术二酮减轻了 BLM 诱导的肺损伤和纤维化。具体来说，莪术二酮显著减轻了 BLM 诱导的小鼠肺中的成纤维细胞向肌成纤维细胞的分化。此外，莪术二酮还降低了 TGF-β1 诱导的成纤维细胞向肌成纤维细胞的分化，表现为α-SMA、胶原 1 和纤连蛋白的表达呈剂量依赖性降低。机制上，莪术二酮抑制 TGF-β1 处理后 Smad3 的磷酸化，从而抑制成纤维细胞分化。
总之，莪术二酮通过抑制成纤维细胞向肌成纤维细胞的分化对肺纤维化发挥治疗作用。由于莪术二酮在 BLM 诱导的小鼠模型中表现出安全性和良好的耐受性，因此莪术二酮可能对开发 IPF 的新型治疗方法有用。
