Unveiling pharmacological targets of Rihimaside C for radiation-induced lung injury: An in silico and experimental integrated approach

IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Youyi Liu , Jingrou Guo , Chuang Liu , Xingyi Chen , Yifei Tang , Minchen Wu , Jianfeng Huang
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Abstract

Background and aim

Radiation-induced lung injury (RILI) is a common complication during caner radiotherapy, mainly characterized by oxidative stress and inflammation. Rihimaside C, a novel dihydroflavonol compound isolated from Ribes himalense, exhibits significant anti-inflammatory and antioxidant properties. The study aims to investigate the therapeutic efficacy of Rihimaside C in treating RILI, as well as to uncover the potential targets and mechanisms involved.

Experimental procedure

Animal experiments were performed to evaluate the pharmacological efficacy of Rihimaside C for RILI. A computer-based strategy was employed to retrieve and screen potential targets for the therapy of Rihimaside C against RILI. STRING, DAVID databases, and Cytoscape software were utilized to construct a protein-protein interaction network and identify hub targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to illuminate the underlying mechanisms. Molecular docking and Cellular Thermal Shift Assay (CETSA) were performed to further validate the hub targets.

Results and conclusion

The results of animal experiments showed that Rihimaside C effectively alleviated RILI. Four hub targets (TNF, HSP90AA1, ESR1 and HIF1A) among the 72 possible targets of Rihimaside C involved in the treatment of RILI were finally identified through network pharmacology, which were enriched in MAPK, IL-17, and PI3K/Akt signaling pathways. Molecular docking and CETSA analyses indicated that HSP90AA1 displayed highest binding affinity with Rihimaside C. This study investigated the therapeutic effects of Rihimaside C on RILI and identified potential targets, providing a novel strategy in treating RILI.

Abstract Image

揭示rihimside C对辐射性肺损伤的药理学靶点:一种计算机与实验相结合的方法
背景与目的放射性肺损伤(RILI)是癌症放疗过程中常见的并发症,主要表现为氧化应激和炎症反应。Rihimaside C是一种从喜马拉雅梨中分离得到的新型二氢黄酮醇化合物,具有显著的抗炎和抗氧化作用。本研究旨在探讨Rihimaside C治疗RILI的疗效,并揭示其潜在的靶点和机制。实验方法:采用动物实验评价利希美赛C对RILI的药理作用。采用计算机为基础的策略来检索和筛选Rihimaside C治疗RILI的潜在靶点。利用STRING、DAVID数据库和Cytoscape软件构建蛋白相互作用网络并鉴定枢纽靶点。通过基因本体和京都基因与基因组百科全书的富集分析来阐明其潜在的机制。进行分子对接和细胞热移实验(CETSA)进一步验证枢纽靶点。结果与结论动物实验结果表明,利希曼苷C能有效缓解RILI。通过网络药理学最终确定了Rihimaside C参与RILI治疗的72个可能靶点中的4个枢纽靶点(TNF、HSP90AA1、ESR1和HIF1A),它们富集于MAPK、IL-17和PI3K/Akt信号通路中。分子对接和CETSA分析表明,HSP90AA1与Rihimaside C的结合亲和力最高。本研究探讨了Rihimaside C对RILI的治疗作用,并确定了潜在靶点,为RILI的治疗提供了新的策略。
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来源期刊
Journal of Traditional and Complementary Medicine
Journal of Traditional and Complementary Medicine Medicine-Complementary and Alternative Medicine
CiteScore
9.30
自引率
6.70%
发文量
78
审稿时长
66 days
期刊介绍: eJTCM is committed to publish research providing the biological and clinical grounds for using Traditional and Complementary Medical treatments as well as studies that demonstrate the pathophysiological and molecular/biochemical bases supporting the effectiveness of such treatments. Review articles are by invitation only. eJTCM is receiving an increasing amount of submission, and we need to adopt more stringent criteria to select the articles that can be considered for peer review. Note that eJTCM is striving to increase the quality and medical relevance of the publications.
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