Park Sa-Yoon, Lee Yoon Yeol, Kim Min Hee, Kim Chang-Eop
Department of Physiology, College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
Life (Basel). 2024 Apr 25;14(5):553. doi: 10.3390/life14050553.
Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients' quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its multi-compound, multi-target herbal medicines (medicinal plants), offers a promising alternative. However, the complexity of these multi-compound traits poses challenges in understanding the overall mechanisms and efficacy of herbal medicines. Here, we demonstrate the efficacy and underlying mechanisms of these multi-compound herbal medicines specifically used for AR at a systemic level. We utilized a modified term frequency-inverse document frequency method to select AR-specific herbs and constructed an herb-compound-target network using reliable databases and computational methods, such as the Quantitative Estimate of Drug-likeness for compound filtering, STITCH database for compound-target interaction prediction (with a high confidence score threshold of 0.7), and DisGeNET and CTD databases for disease-gene association analysis. Through this network, we conducted AR-related targets and pathway analyses, as well as clustering analysis based on target-level information of the herbs. Gene ontology enrichment analysis was conducted using a protein-protein interaction network. Our research identified 14 AR-specific herbs and analyzed whether AR-specific herbs are highly related to previously known AR-related genes and pathways. AR-specific herbs were found to target several genes related to inflammation and AR pathogenesis, such as PTGS2, HRH1, and TBXA2R. Pathway analysis revealed that AR-specific herbs were associated with multiple AR-related pathways, including cytokine signaling, immune response, and allergic inflammation. Additionally, clustering analysis based on target similarity identified three distinct subgroups of AR-specific herbs, corroborated by a protein-protein interaction network. Group 1 herbs were associated with the regulation of inflammatory responses to antigenic stimuli, while Group 2 herbs were related to the detection of chemical stimuli involved in the sensory perception of bitter taste. Group 3 herbs were distinctly associated with antigen processing and presentation and NIK/NF-kappa B signaling. This study decodes the principles of TAM herbal configurations for AR using a network pharmacological approach, providing a holistic understanding of drug effects beyond specific pathways.
变应性鼻炎（AR）是一种全身性变应性疾病，对患者的生活质量有相当大的影响。目前的治疗方法包括抗组胺药和鼻用类固醇；然而，长期使用这些药物往往会产生不良副作用。在此背景下，传统亚洲医学（TAM）及其多成分、多靶点的草药（药用植物）提供了一种有前景的替代方案。然而，这些多成分特性的复杂性给理解草药的整体作用机制和疗效带来了挑战。在此，我们在系统层面展示了这些专门用于AR的多成分草药的疗效及其潜在机制。我们利用一种改进的词频-逆文档频率方法来选择AR特异性草药，并使用可靠的数据库和计算方法构建了一个草药-化合物-靶点网络，例如用于化合物筛选的类药性质定量评估、用于化合物-靶点相互作用预测的STITCH数据库（高置信度得分阈值为0.7），以及用于疾病-基因关联分析的DisGeNET和CTD数据库。通过这个网络，我们进行了AR相关靶点和通路分析，以及基于草药靶点水平信息的聚类分析。使用蛋白质-蛋白质相互作用网络进行基因本体富集分析。我们的研究确定了14种AR特异性草药，并分析了AR特异性草药是否与先前已知的AR相关基因和通路高度相关。发现AR特异性草药靶向几个与炎症和AR发病机制相关的基因，如PTGS2、HRH1和TBXA2R。通路分析表明，AR特异性草药与多个AR相关通路有关，包括细胞因子信号传导、免疫反应和变应性炎症。此外，基于靶点相似性的聚类分析确定了AR特异性草药有三个不同的亚组，这得到了蛋白质-蛋白质相互作用网络的证实。第1组草药与对抗抗原刺激的炎症反应调节有关，而第2组草药与参与苦味感官感知的化学刺激检测有关。第3组草药与抗原加工和呈递以及NIK/NF-κB信号传导明显相关。本研究使用网络药理学方法解读了TAM治疗AR的草药配方原则，提供了对药物作用超越特定通路的整体理解。
