Department of Respiratory Medicine, Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun 130021, Jilin, P.R. China.
Food Funct. 2021 Apr 7;12(7):3120-3131. doi: 10.1039/d0fo01583k. Epub 2021 Mar 16.
Asthma is one of the most common illnesses associated with chronic airway inflammation; however, there are currently no effective therapies apart from glucocorticoids. Zingerone (ZIN), an active compound isolated from ginger, has been reported to have a broad spectrum of pharmacological properties. In this study, Zingerone was administrated to HO-stimulated mouse airway epithelial cell line MLE12 cells and asthmatic mice. The concentration of cytokines was evaluated using enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE), Periodic Acid-Schiff (PAS) and Masson staining were used for histological analyses. Protein levels in cells or lung tissues were determined using western blot, immunohistochemistry staining. The results showed that treatment with Zingerone dramatically inhibited oxidative stress and the inflammatory response in MLE12 cells stimulated with HO and asthmatic mice. Furthermore, Zingerone treatment could decrease the expression of phosphorylated (p)-IκBα and p65 (nuclear) and increase the expression of phosphorylation of AMP-activated protein kinase (p-AMPK), nuclear factor erythroid-2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) to alleviate oxidative damage and inflammation both in vivo and in vitro. In addition, Zingerone treatment reduced the exudation and infiltration of inflammatory cells and suppressed goblet cell hyperplasia in a murine asthma model. Treatment with Zingerone also decreased the level of interleukin (IL)-4, IL-5, IL-13, and increased the level of interferon gamma (IFN-γ) in the BALF and attenuated airway hyperresponsiveness (AHR). However, inhibition of AMPK or Nrf2 suppressed the cellular protective, antioxidative, and anti-inflammatory properties of Zingerone. Taken together, these results demonstrate that Zingerone possesses the potential to relieve asthma via upregulating the AMPK/Nrf2/HO-1 signaling pathway.
哮喘是与慢性气道炎症相关的最常见疾病之一；然而，除了糖皮质激素外，目前尚无有效的治疗方法。姜酮（ZIN）是从生姜中分离得到的一种活性化合物，据报道具有广泛的药理作用。在这项研究中，姜酮被给予 HO 刺激的小鼠气道上皮细胞系 MLE12 细胞和哮喘小鼠。使用酶联免疫吸附测定（ELISA）评估细胞因子的浓度。使用苏木精-伊红（HE）、过碘酸-希夫（PAS）和 Masson 染色进行组织学分析。使用 Western blot、免疫组织化学染色测定细胞或肺组织中的蛋白水平。结果表明，Zingerone 处理可显著抑制 HO 刺激的 MLE12 细胞和哮喘小鼠的氧化应激和炎症反应。此外，Zingerone 处理可降低磷酸化（p）-IκBα 和 p65（核）的表达，并增加磷酸化 AMP 激活蛋白激酶（p-AMPK）、核因子红细胞 2 相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）的表达，以减轻体内和体外的氧化损伤和炎症。此外，Zingerone 处理可减少炎症细胞的渗出和浸润，并抑制哮喘小鼠模型中杯状细胞的增生。Zingerone 处理还降低了 BALF 中的白细胞介素（IL）-4、IL-5、IL-13 水平，并增加了干扰素γ（IFN-γ）水平，从而减轻了气道高反应性（AHR）。然而，AMPK 或 Nrf2 的抑制抑制了 Zingerone 的细胞保护、抗氧化和抗炎特性。总之，这些结果表明 Zingerone 通过上调 AMPK/Nrf2/HO-1 信号通路具有缓解哮喘的潜力。
