Zhang Xiaohua, Xiong Dayan, Deng Lang, Qian Rui, Tang Siyuan, Liu Wei, Li Yin, Liu Lang, Xie Weixi, Lin Miao
Department of Occupational Medicine, Hunan Prevention and Treatment Institute for Occupational Diseases, Changsha, China.
Xiangya Nursing School, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, China.
Sci Rep. 2025 Aug 25;15(1):31306. doi: 10.1038/s41598-025-17045-7.
Idiopathic pulmonary fibrosis (IPF) is an interstitial fibrotic lung disease characterized by myofibroblast differentiation and collagen deposition. Excessive activation of fibroblasts in the lungs leads to severe alveolar dysfunction and tissue destruction seen by histological assessment. IPF presents a high mortality rate, limited therapeutic options, and an intense need to develop safe and effective therapeutic drugs. Lysionotin is a flavonoid isolated from herbal extracts with various biological effects such as anti-tuberculosis mycobacteria and anti-inflammatory. Nevertheless, its effect on pulmonary fibrosis is not known. This study aims to investigate the effect of Lysionotin on bleomycin (BLM)-induced pulmonary fibrosis and its mechanism. We used BLM to establish a mouse model of pulmonary fibrosis and injected Lysionotin intraperitoneally on days 15-28 to observe its effect on pulmonary fibrosis. The molecular mechanism of Lysionotin was investigated in vitro using transforming growth factor-β (TGF-β) induced myofibroblasts. Lysionotin attenuates TGF-β-induced myofibroblast differentiation and oxidative stress by promoting nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream expression of antioxidant genes NAD(P)H quinone dehydrogenase 1 (NQO-1) and heme oxygenase 1 (HO-1) by activating AMP-activated protein kinase (AMPK). Lysionotin exerts anti-pulmonary fibrosis effects by regulating myofibroblast differentiation and reducing oxidative stress through the AMPK/Nrf2 pathway, illustrating the potential significance of Lysionotin in protecting against BLM-induced pulmonary fibrosis.
特发性肺纤维化（IPF）是一种间质性纤维化肺病，其特征为肌成纤维细胞分化和胶原蛋白沉积。肺部成纤维细胞的过度活化会导致严重的肺泡功能障碍和组织破坏，这在组织学评估中可见。IPF具有高死亡率、有限的治疗选择，并且迫切需要开发安全有效的治疗药物。来苏诺汀是一种从草药提取物中分离出的黄酮类化合物，具有多种生物学效应，如抗结核分枝杆菌和抗炎作用。然而，其对肺纤维化的影响尚不清楚。本研究旨在探讨来苏诺汀对博来霉素（BLM）诱导的肺纤维化的影响及其机制。我们使用BLM建立了肺纤维化小鼠模型，并在第15至28天腹腔注射来苏诺汀，以观察其对肺纤维化的影响。使用转化生长因子-β（TGF-β）诱导的肌成纤维细胞在体外研究来苏诺汀的分子机制。来苏诺汀通过激活AMP活化蛋白激酶（AMPK）促进核因子红细胞2相关因子2（Nrf2）及其下游抗氧化基因NAD（P）H醌脱氢酶1（NQO-1）和血红素加氧酶1（HO-1）的表达，从而减轻TGF-β诱导的肌成纤维细胞分化和氧化应激。来苏诺汀通过调节肌成纤维细胞分化并通过AMPK/Nrf2途径降低氧化应激来发挥抗肺纤维化作用，这说明了来苏诺汀在预防BLM诱导的肺纤维化中的潜在意义。
