Objectives: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms.
Methods: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting.
Results: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727).
Conclusions: Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
目的: 探讨积雪草抗银屑病活性成分及其作用机制。方法: 利用TCMSP、PharmMapper等数据库获取积雪草化合物和靶点，利用GeneCards数据库筛选银屑病相关的潜在靶点，Cytoscape 3.10.0软件导入积雪草活性成分、银屑病共同靶点制作“药物-活性成分-作用靶点”网络图，使用STRING数据库构建PPI网络，借助DAVID数据库进行通路富集分析。通过网络药理学筛选得到积雪草主要活性成分槲皮素、积雪草苷、积雪草酸，并将这3种活性成分（7.5、15、30、60 μmol/L）作用于脂多糖（LPS）刺激RAW264.7小鼠巨噬细胞炎症模型，Griess法检测细胞NO水平评价抗炎活性。ELISA检测TNF-α、IL-6细胞促炎因子的表达，RT-qPCR测定细胞IL-23、IL-17A、TNF-α、IL-6 mRNA的表达，Western blotting检测细胞p-STAT3（Tyr705）、p-STAT3（Ser727）的表达变化。结果: 网络药理学研究分析获取积雪草靶点139个，银屑病靶点4604个，PPI网络图显示CASP3、EGFR、PTGS2和ESR1为治疗银屑病的关键靶点，分析得到槲皮素、积雪草苷、积雪草酸可能是积雪草抗银屑病关键活性成分。KEGG结果显示与癌症、IL-17以及MAPK信号通路相关。槲皮素、积雪草苷、积雪草酸处理细胞炎症模型，发现槲皮素表现出明显的抗炎活性，细胞NO水平降低（P<0.05）。与LPS组相比，槲皮素处理后细胞中TNF-α，IL-6促炎因子分泌减少（P<0.05），IL-23、IL-17A、TNF-α、IL-6 mRNA表达水平降低（P<0.05），STAT3磷酸化的两个位点（Tyr705、Ser727）蛋白表达均明显下调（P<0.05）。结论: 积雪草抗银屑病主要活性成分为槲皮素、积雪草苷和积雪草酸，其中关键成分槲皮素通过抑制NO产生、炎症因子TNF-α、IL-6的表达，并通过介导STAT3磷酸化调控IL-23/IL-17A炎症轴抑制炎症反应发挥抗银屑病作用。.
Keywords: Centella asiatica; IL-23/IL-17A; network pharmacology; psoriasis; quercetin.