Institute of Literature in Chinese Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing City, Jiangsu Province, China.
Department of Pediatrics, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Nov;397(11):8979-8992. doi: 10.1007/s00210-024-03170-z. Epub 2024 Jun 14.
Pulmonary fibrosis (PF) is a persistent interstitial lung condition for which effective treatment options are currently lacking. Zerumbone (zerum), a humulane sesquiterpenoid extracted from Zingiber zerumbet Smith, has been documented in previous studies to possess various pharmacological benefits. The aim of this study was to observe and investigate the therapeutic effects and mechanisms of zerum on pulmonary fibrosis. We utilized a transforming growth factor (TGF)-β1-induced human lung fibroblast (MRC-5) activation model and a bleomycin-induced pulmonary fibrosis mouse model. Cell counting kit 8 (CCK8) and cell migration assays were performed to assess the effects of zerum on MRC-5 cells. Masson's trichrome, Hematoxylin and Eosin (HE), and Sirius Red staining were conducted for pathological evaluation of lung tissue. Western blot experiments were conducted to measure the protein expression levels of Collagen I, α-SMA, Nrf2, and SIRT1. Immunofluorescence and immunohistochemistry assays were used to detect the expression of reactive oxygen species (ROS), Nrf2, and α-SMA. ELISA was employed to measure the levels of MDA, SOD, and GSH-Px. Our findings from in vitro and in vivo studies demonstrated that zerum significantly inhibited the migration ability of TGF-β1-induced MRC-5 cells, reduced ROS production in TGF-β1-induced MRC-5 cells and pulmonary fibrosis mice, and decreased the expression of Collagen I and α-SMA proteins. Additionally, zerum activated the SIRT1/Nrf2 signaling pathway in TGF-β1-induced MRC-5 cells and pulmonary fibrosis mice. Knockdown of SIRT1 abolished the anti-fibrotic effects of zerum. These results suggest that zerum inhibits TGF-β1 and BLM-induced cell and mouse pulmonary fibrosis by activating the SIRT1/Nrf2 pathway.
肺纤维化（PF）是一种持续的间质性肺病，目前缺乏有效的治疗方法。姜烯（zerum）是从姜黄属姜黄中提取的一种倍半萜烯，以前的研究已经证明它具有多种药理学益处。本研究旨在观察和研究姜烯对肺纤维化的治疗作用和机制。我们利用转化生长因子（TGF）-β1诱导的人肺成纤维细胞（MRC-5）激活模型和博来霉素诱导的肺纤维化小鼠模型。通过细胞计数试剂盒 8（CCK8）和细胞迁移实验评估姜烯对 MRC-5 细胞的影响。进行 Masson 三色、苏木精和伊红（HE）和天狼星红染色以评估肺组织的病理变化。进行 Western blot 实验以测量胶原 I、α-SMA、Nrf2 和 SIRT1 的蛋白表达水平。免疫荧光和免疫组化实验用于检测活性氧（ROS）、Nrf2 和 α-SMA 的表达。ELISA 用于测量 MDA、SOD 和 GSH-Px 的水平。我们的体外和体内研究结果表明，姜烯显著抑制 TGF-β1 诱导的 MRC-5 细胞的迁移能力，减少 TGF-β1 诱导的 MRC-5 细胞和肺纤维化小鼠中的 ROS 产生，并降低胶原 I 和 α-SMA 蛋白的表达。此外，姜烯在 TGF-β1 诱导的 MRC-5 细胞和肺纤维化小鼠中激活了 SIRT1/Nrf2 信号通路。SIRT1 的敲低消除了姜烯的抗纤维化作用。这些结果表明，姜烯通过激活 SIRT1/Nrf2 通路抑制 TGF-β1 和 BLM 诱导的细胞和小鼠肺纤维化。
