Chenxi Yang , Chenglin Song , Yi Wang , Wencheng Zhou , Wei Zheng , Han Zhou , Guoliang Deng , Haibo Li , Wei Xiao , Zhongqi Yang , Lingdong Kong , Huiming Ge , Yaohong Song , Yang Sun
{"title":"Re-Du-Ning injection ameliorates radiation-induced pneumonitis and fibrosis by inhibiting AIM2 inflammasome and epithelial-mesenchymal transition.","authors":"Chenxi Yang , Chenglin Song , Yi Wang , Wencheng Zhou , Wei Zheng , Han Zhou , Guoliang Deng , Haibo Li , Wei Xiao , Zhongqi Yang , Lingdong Kong , Huiming Ge , Yaohong Song , Yang Sun","doi":"10.1016/j.phymed.2022.154184","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Radiation-induced lung injury (RILI) is a common side effect in chest radiotherapy patients, and there is no good medicine to treat it. Re-Du-Ning (RDN) injection is a traditional Chinese medicine<span> that is clinically used to treat upper respiratory tract infections<span> and acute bronchitis. RDN has the advantage of high safety and mild side effects. The mechanism of most traditional Chinese medicine preparations is unknown.</span></span></p></div><div><h3>Purpose</h3><p>To illustrate the mechanisms of RDN for the treatment of RILI.</p></div><div><h3>Methods</h3><p><span>Female C57BL/6 mice were used to establish a RILI model via irradiation, and RDN injection was intraperitoneally administered at doses of 5, 10, and 20 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to Absent in </span>melanoma<span> 2 (AIM2) inflammasome<span><span> were analyzed via ELISA and a network pharmacological approach. In addition, the data related to epithelial-mesenchymal transition (EMT) were analyzed via immunofluorescence, </span>Western blotting, and a network pharmacological approach.</span></span></p></div><div><h3>Results</h3><p><span><span>RDN robustly alleviated RILI. Meanwhile, RDN downregulated inflammatory cells’ infiltration and the expression of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. Next, the potential molecular mechanisms of RDN were predicted through network pharmacology analysis. RDN may ameliorate </span>radiation pneumonitis<span> (RP) by inhibiting AIM2-mediated pyroptosis. Moreover, RDN treatment inhibited EMT and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway. The active compounds from </span></span><span><em>Lonicera japonica</em></span> Thunb. decreased the phosphorylation of Akt.</p></div><div><h3>Conclusion</h3><p>These findings demonstrate that RDN, as a traditional Chinese medicine preparation, will be a candidate drug for treating RILI.</p></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"10","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711322002628","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 10
Abstract
Background
Radiation-induced lung injury (RILI) is a common side effect in chest radiotherapy patients, and there is no good medicine to treat it. Re-Du-Ning (RDN) injection is a traditional Chinese medicine that is clinically used to treat upper respiratory tract infections and acute bronchitis. RDN has the advantage of high safety and mild side effects. The mechanism of most traditional Chinese medicine preparations is unknown.
Purpose
To illustrate the mechanisms of RDN for the treatment of RILI.
Methods
Female C57BL/6 mice were used to establish a RILI model via irradiation, and RDN injection was intraperitoneally administered at doses of 5, 10, and 20 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to Absent in melanoma 2 (AIM2) inflammasome were analyzed via ELISA and a network pharmacological approach. In addition, the data related to epithelial-mesenchymal transition (EMT) were analyzed via immunofluorescence, Western blotting, and a network pharmacological approach.
Results
RDN robustly alleviated RILI. Meanwhile, RDN downregulated inflammatory cells’ infiltration and the expression of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. Next, the potential molecular mechanisms of RDN were predicted through network pharmacology analysis. RDN may ameliorate radiation pneumonitis (RP) by inhibiting AIM2-mediated pyroptosis. Moreover, RDN treatment inhibited EMT and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway. The active compounds from Lonicera japonica Thunb. decreased the phosphorylation of Akt.
Conclusion
These findings demonstrate that RDN, as a traditional Chinese medicine preparation, will be a candidate drug for treating RILI.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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