Oridonin attenuates carrageenan-induced pleurisy via activation of the KEAP-1/Nrf2 pathway and inhibition of the TXNIP/NLRP3 and NF-κB pathway in mice
Autor: | Jingbo Huang, Huahong Yang, Yanli Gao, Liping Peng, Zhongmei Wen, Xinxin Ci |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Inflammasomes NF-E2-Related Factor 2 viruses Immunology Anti-Inflammatory Agents Pharmacology Carrageenan medicine.disease_cause Antioxidants Pathogenesis Mice 03 medical and health sciences chemistry.chemical_compound Thioredoxins 0302 clinical medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Pharmacology (medical) Pleurisy Mice Inbred BALB C Kelch-Like ECH-Associated Protein 1 Chemistry NF-kappa B Inflammasome NF-κB Glutathione biochemical phenomena metabolism and nutrition medicine.disease Disease Models Animal 030104 developmental biology Female Carrier Proteins Diterpenes Kaurane 030217 neurology & neurosurgery TXNIP Oxidative stress medicine.drug |
Zdroj: | Inflammopharmacology. 28:513-523 |
ISSN: | 1568-5608 0925-4692 |
Popis: | The classic NLRP3 inflammasome and NF-κB molecular pathways are activated in many inflammatory-related diseases, such as pleurisy. Because oridonin (Ori) has been indicated as a covalent NLRP3 inhibitor with strong anti-inflammasome activity, we herein aimed to assess the effects of Ori in a mouse model of carrageenan (CAR)-induced pleurisy. The results showed that CAR caused hemorrhaging and exudation of lung tissues and the release of inflammatory factors (TNF-α, IL-6 and IL-1β), effects that were significantly reduced by treatment with Ori. In addition, increased neutrophil infiltration, protein concentrations and volumes were found in the exudates of the CAR group, and these phenomena were suppressed by Ori treatment. Regarding cellular pathways, Ori could alleviate the CAR-activated NF-κB and TXNIP/NLRP3 pathways. Additionally, oxidative stress was shown to be involved in the pathogenesis of pleurisy, but possible mechanisms remain to be explored. Herein, Ori reversed the CAR-induced depletion of GSH and SOD and the CAR-induced increases in ROS, MPO and MDA levels. Furthermore, Ori inhibited NOX-4 levels, initiated the dissociation of KEAP-1 from Nrf2, activated the downstream genes HO-1 and exerted antioxidative effects on CAR-induced pleurisy. In conclusion, Ori conferred protection against CAR-induced pleurisy via Nrf2-dependent antioxidative and NLRP3-dependent anti-inflammatory properties. |
Databáze: | OpenAIRE |
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