Re-Du-Ning injection ameliorates radiation-induced pneumonitis and fibrosis by inhibiting AIM2 inflammasome and epithelial-mesenchymal transition.

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2022-07-20 DOI:10.1016/j.phymed.2022.154184

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

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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.

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热毒宁注射液通过抑制AIM2炎性体和上皮-间质转化改善辐射性肺炎和纤维化。

背景:辐射致肺损伤(RILI)是胸部放疗患者常见的副作用，目前还没有很好的药物可以治疗。热毒宁注射液是临床上用于治疗上呼吸道感染和急性支气管炎的中药。RDN具有安全性高、副作用轻的优点。大多数中药制剂的作用机理尚不清楚。目的探讨RDN治疗RILI的机制。方法以C57BL/6雌性小鼠为模型，分别以5、10、20 ml/kg剂量腹腔注射RDN。采用ELISA和qPCR检测细胞因子。通过ELISA和网络药理学方法分析与黑色素瘤2 (AIM2)炎症小体相关的数据。此外，通过免疫荧光、Western blotting和网络药理学方法分析与上皮-间质转化(EMT)相关的数据。结果rdn对RILI有明显的缓解作用。同时，RDN下调炎症细胞的浸润及促炎细胞因子IL-1β、IL-6、TNF-α的表达。其次，通过网络药理学分析预测RDN的潜在分子机制。RDN可能通过抑制aim2介导的焦亡来改善放射性肺炎(RP)。此外，RDN处理抑制EMT和PI3K /蛋白激酶B (AKT)通路。金银花中有效成分的研究。降低Akt磷酸化水平。结论RDN作为中药制剂，有望成为治疗RILI的候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

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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