School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.
School of Basic Medical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, P.R. China
Clin Sci (Lond). 2019 Jul 15;133(13):1523-1536. doi: 10.1042/CS20190331.
Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in (), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both and Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both and , whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both and Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured on COPD patients.
香烟烟雾（CS）是慢性阻塞性肺疾病（COPD）的主要原因。CS 会加剧炎症、氧化应激和细胞凋亡。麦角甾醇是一种传统药用植物，用于治疗各种疾病的主要生物活性成分。本工作旨在研究麦角甾醇对香烟烟雾提取物（CSE）诱导的 COPD 模型中抗炎、抗氧化应激和抗细胞凋亡的作用。我们的结果表明，CSE 通过核因子 kappa B（NF-κB）/p65 通路诱导炎症和氧化应激以及凋亡，涉及 Bcl-2 家族蛋白，在 16HBE 细胞和 Balb/c 小鼠中均如此。CSE 诱导上皮细胞死亡，并增加一氧化氮（NO）、白细胞介素 6（IL-6）、肿瘤坏死因子 α（TNF-α）、丙二醛（MDA）和凋亡相关蛋白裂解 caspase 3/7/9 和裂解多聚（ADP-核糖）聚合酶（PARP）的表达，同时降低超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的水平。麦角甾醇处理 16HBE 细胞和 Balb/c 小鼠可通过抑制 NF-κB/p65 的激活来抑制 CSE 诱导的炎症、氧化应激和凋亡。麦角甾醇通过抑制凋亡相关蛋白的表达来抑制凋亡，无论是在 16HBE 细胞还是在 Balb/c 小鼠中均如此。此外，使用 QNZ（NF-κB 抑制剂）也部分表明，NF-κB/p65 通路参与了麦角甾醇的保护作用。这些结果表明，麦角甾醇通过 NF-κB/p65 通路抑制 COPD 的炎症、氧化应激和凋亡，提示麦角甾醇可能部分负责培养的 对 COPD 患者的治疗作用。
