Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
J Ethnopharmacol. 2022 Jan 30;283:114694. doi: 10.1016/j.jep.2021.114694. Epub 2021 Sep 30.
The flower buds of Tussilago farfara L. (Abbreviated as FTF) were widely used in traditional Chinese medicine (TCM) to treat respiratory diseases, including asthma, dry throat, great thirst, turbid saliva, stinky pus, and coughs caused by various causes.
The aim of study is to explore the efficiency of FTF in vitro and in vivo for the treatment of lung inflammation, and to illustrate the possible mechanisms of FTF in treating inflammation-related respiratory diseases targeting NOD-like receptor 3 (NLRP3) inflammasome, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB).
Lung inflammation model in vivo was induced by exposure of mice to cigarette smoke (CS) for two weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory factors, and histology in lung tissues were investigated in presence or absence of ethanol extract of the flower buds of T. farfara L. (FTF-EtOH). In the cell-based models, nitric oxide (NO) assay, flow cytometry assay, enzyme-linked immunosorbent assay (Elisa), and glutathione (GSH) assay were used to explore the anti-inflammatory and anti-oxidant effects of FTF-EtOH. Possible anti-inflammatory mechanisms of FTF targeting NLRP3 inflammasome, Nrf2, and NF-κB have been determined using western blot, quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence assay, nuclear and cytoplasmic extraction, and ubiqutination assay.
FTF-EtOH suppressed CS-induced overproduction of inflammatory factors [e.g., tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)], and upregulation of the content of intracellular MDA in the lung homogenate of mice. In cell-based models, FTF-EtOH reduced the lipopolysaccharide (LPS)-induced overproduction of inflammatory factors, and attenuated the CS extract-induced overgeneration of reactive oxygen species (ROS). Furthermore, FTF-EtOH up-regulated Nrf2 and its downstream genes through enhancing the stability of Nrf2 protein, and inhibited the activation of NF-κB and NLRP3 inflammasome, which have been confirmed by detecting the protein levels in the mouse model.
FTF-EtOH effectively attenuated lung inflammation in vitro and in vivo. The protection of FTF-EtOH against inflammation was produced by activation of Nrf2 and inhibitions of NF-κB and NLRP3 inflammasome. These datas definitely support the ethnopharmacological use of FTF as an anti-inflammatory drug for treating respiratory diseases in TCM.
款冬花花蕾（简称 FTF）在传统中药（TCM）中被广泛用于治疗呼吸系统疾病，包括哮喘、咽干、口渴、唾液浑浊、臭脓和各种原因引起的咳嗽。
本研究旨在探讨 FTF 在体外和体内治疗肺部炎症的疗效，并阐明 FTF 通过靶向 NOD 样受体 3（NLRP3）炎性小体、核因子红细胞 2 相关因子 2（Nrf2）和核转录因子-κB（NF-κB）治疗炎症相关呼吸系统疾病的可能机制。
通过用香烟烟雾（CS）暴露小鼠两周来诱导体内肺部炎症模型。研究了在存在或不存在款冬花花蕾乙醇提取物（FTF-EtOH）的情况下，肺组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、炎症因子和组织学水平。在基于细胞的模型中，使用一氧化氮（NO）测定、流式细胞术测定、酶联免疫吸附测定（ELISA）和谷胱甘肽（GSH）测定来研究 FTF-EtOH 的抗炎和抗氧化作用。使用 Western blot、实时定量逆转录聚合酶链反应（qRT-PCR）、免疫荧光测定、核和细胞质提取和泛素化测定来确定 FTF 针对 NLRP3 炎性小体、Nrf2 和 NF-κB 的抗炎机制。
FTF-EtOH 抑制 CS 诱导的炎症因子（如肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β））过度产生，以及肺匀浆中 MDA 含量的上调。在基于细胞的模型中，FTF-EtOH 减少了脂多糖（LPS）诱导的炎症因子过度产生，并减轻了 CS 提取物诱导的活性氧（ROS）过度产生。此外，FTF-EtOH 通过增强 Nrf2 蛋白的稳定性来上调 Nrf2 及其下游基因，并抑制 NF-κB 和 NLRP3 炎性小体的激活，这在小鼠模型中通过检测蛋白水平得到了证实。
FTF-EtOH 有效减轻了体内外肺部炎症。FTF-EtOH 对炎症的保护作用是通过激活 Nrf2 以及抑制 NF-κB 和 NLRP3 炎性小体来实现的。这些数据肯定支持了款冬花在 TCM 中作为治疗呼吸系统疾病的抗炎药物的民族药理学用途。
