Liu Pingping, Zeng Linna, Fu Hongyun, Li Fuzhu
Emergency Medicine Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421000, People's Republic of China.
Department of Endocrinology, The Third People's Hospital of Yongzhou, Yongzhou, Hunan, 425000, People's Republic of China.
Infect Drug Resist. 2025 Jul 3;18:3257-3277. doi: 10.2147/IDR.S499975. eCollection 2025.
Sepsis is a critical condition characterized by an atypical immune response to infection, resulting in systemic inflammatory response syndrome. Honeysuckle, a traditional Chinese medicinal plant with anti-inflammatory, anti-tumor, and antioxidant characteristics, shows promise in mitigating sepsis-related inflammatory responses. The precise mechanism by which honeysuckle confers protection against sepsis remains uncertain. This research utilized network pharmacology to explore the mechanisms through which honeysuckle mitigates sepsis.
Bioactive compounds of honeysuckle were sourced from the Traditional Chinese Medicine System Pharmacology database, and their corresponding targets were identified. Sepsis-associated genes were gathered from the GeneCards and Online Mendelian Inheritance in Man databases. The regulatory network depicting "active ingredients-target" relationships was constructed utilizing Cytoscape 3.9.1 software. Target genes affected by honeysuckle in sepsis were analyzed utilizing the String database to create a protein-protein interaction network. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed through the Database for Annotation, Visualization, and Integrated Discovery platform, aiming to identify pathways associated with these pivotal targets. Subsequently, molecular docking confirmed the binding capacity of these bioactive ingredients to pivotal targets. Subsequent in vitro experiments were conducted for additional validation. Network pharmacology analysis employed R software for extensive data processing. A Student's -test compared the mean values of the two groups in the in vitro experimental data. Statistical analysis for multiple group comparisons was carried out utilizing one-way ANOVA, with Tukey's post hoc test applied for further analysis.
The screening process identified 23 active ingredients in honeysuckle, which are linked to 291 targets. Molecular docking demonstrated strong binding affinities of kaempferol, luteolin, and quercetin to the target proteins TP53, TLR4, and MYD88. In vitro experiments demonstrated that honeysuckle and its active components mitigate sepsis by inhibiting the TLR4/MYD88 signaling pathways, thereby reducing proinflammatory cytokine production.
These findings indicate that honeysuckle may be an effective treatment for sepsis by modulating key proteins such as TP53, TLR4, and MYD88.
脓毒症是一种危急病症，其特征是对感染产生非典型免疫反应，导致全身炎症反应综合征。金银花是一种具有抗炎、抗肿瘤和抗氧化特性的传统中药植物，在减轻脓毒症相关炎症反应方面显示出前景。金银花赋予抗脓毒症保护作用的确切机制仍不确定。本研究利用网络药理学探索金银花减轻脓毒症的机制。
金银花的生物活性化合物来源于中药系统药理学数据库，并确定其相应靶点。脓毒症相关基因从基因卡片数据库和人类孟德尔遗传在线数据库收集。利用Cytoscape 3.9.1软件构建描绘“活性成分-靶点”关系的调控网络。利用String数据库分析金银花在脓毒症中影响的靶基因，以创建蛋白质-蛋白质相互作用网络。通过注释、可视化和综合发现数据库平台进行京都基因与基因组百科全书和基因本体分析，旨在识别与这些关键靶点相关的途径。随后，分子对接证实了这些生物活性成分与关键靶点的结合能力。随后进行体外实验以作进一步验证。网络药理学分析使用R软件进行大量数据处理。体外实验数据中两组的平均值采用学生t检验进行比较。多组比较的统计分析采用单因素方差分析，并应用Tukey事后检验进行进一步分析。
筛选过程确定了金银花中的23种活性成分，它们与291个靶点相关。分子对接表明，山奈酚、木犀草素和槲皮素与靶蛋白TP53、TLR4和MYD88具有很强的结合亲和力。体外实验表明，金银花及其活性成分通过抑制TLR4/MYD88信号通路减轻脓毒症，并因此减少促炎细胞因子的产生。
这些发现表明，金银花可能通过调节TP53、TLR4和MYD88等关键蛋白成为治疗脓毒症的有效药物。
