State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China.
Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, 157 Daming Road, Nanjing, Jiangsu, 210012 China.
Phytomedicine. 2022 Jul 20;102:154184. doi: 10.1016/j.phymed.2022.154184. Epub 2022 May 21.
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.
To illustrate the mechanisms of RDN for the treatment of RILI.
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.
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.
These findings demonstrate that RDN, as a traditional Chinese medicine preparation, will be a candidate drug for treating RILI.
放射性肺损伤（RILI）是胸部放射治疗患者的常见副作用，目前尚无治疗它的良药。热毒宁注射液是一种中药，临床上用于治疗上呼吸道感染和急性支气管炎。热毒宁注射液具有安全性高、副作用小的优点。大多数中药制剂的作用机制尚不清楚。
阐明热毒宁注射液治疗 RILI 的作用机制。
采用雌性 C57BL/6 小鼠建立 RILI 模型，通过腹腔注射热毒宁注射液，剂量分别为 5、10 和 20ml/kg。通过 ELISA 和 qPCR 测定细胞因子。通过 ELISA 和网络药理学方法分析与缺失黑色素瘤 2（AIM2）炎性小体相关的数据。此外，通过免疫荧光、Western blot 和网络药理学方法分析与上皮-间充质转化（EMT）相关的数据。
热毒宁注射液可显著缓解 RILI。同时，热毒宁注射液下调了炎症细胞浸润和促炎细胞因子（如 IL-1β、IL-6 和 TNF-α）的表达。接下来，通过网络药理学分析预测了热毒宁注射液的潜在分子机制。热毒宁注射液可能通过抑制 AIM2 介导的细胞焦亡来改善放射性肺炎（RP）。此外，热毒宁注射液治疗抑制了 EMT 和磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）通路。金银花中的活性化合物降低了 Akt 的磷酸化。
这些发现表明，热毒宁注射液作为一种中药制剂，将成为治疗 RILI 的候选药物。
