背景:上呼吸道感染(URTI),最常见的呼吸道疾病之一,年发病率很高。在中国,金莲花胶囊已用于治疗URTI。然而,潜在机制尚不清楚.
方法:采用网络药理学方法探讨金莲花胶囊治疗URTI的潜在作用机制。金莲花中的活性化合物是从TCMSP中获得的,SymMap,和ETCM数据库。TCMSP,PubChem,和SwissTargetPrediction数据库用于预测金莲花的潜在靶标。与URTI相关的目标是从GeneCards和DisGeNet数据库中收集的。通过网络拓扑选择与URTI相关的关键靶标和信号通路。GO,和KEGG途径富集分析。分子对接用于验证活性化合物与关键靶标之间的结合活性。
结果:槲皮素,果胶素,β-谷甾醇,刺槐素和环加素是金莲花胶囊中的主要活性化合物。确认了81个候选治疗靶标参与了金莲花胶囊对URTI的保护。其中,7个关键靶标(TP53、IL6、AKT1、CASS3、CXCL8、MMP9和EGFR)被证实对主要活性化合物具有良好的结合亲和力。此外,富集分析表明炎症反应,病毒感染和氧化应激相关的生物学过程和途径可能是潜在的机制。
结论:总体而言,本研究澄清了槲皮素,果胶素,β-谷甾醇,刺槐素和环加素被证明是金莲花胶囊治疗URTI的主要有效化合物,可能通过作用于IL6、AKT1、CASP3、CXCL8、MMP9和EGFR的靶点发挥抗感染作用,抗病毒,和抗氧化作用。本研究从网络药理学的角度为金莲花胶囊治疗URTI的活性成分和作用机制提供了新的认识。
BACKGROUND: Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear.
METHODS: Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets.
RESULTS: Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism.
CONCLUSIONS: Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.