基于网络药理学研究雷公藤抗肝癌的分子机制及初步验证

基于中药系统药理学数据库与分析平台（TCMSP）筛选雷公藤抗肝癌的有效成分，采用GeneCards、OMIM、Drugbank、GEO等疾病数据库筛选差异性表达基因，找到相互映射的核心物质及靶点，构建药效成分-靶点（C-T）网络、蛋白互作网络（PPI），进行gene ontology （GO）和Kyoto encyclopedia of genes and genomes （KEGG）富集分析，获知其生物学机制，并利用分子对接技术和生物学实验进行验证。结果表明，雷公藤的主要药效成分为雷公藤甲素和雷公藤红素，PTGS2、CXCL8、TGFB1、STAT3等核心靶点主要富集于癌症及多条炎症因子的相关通路中，雷公藤甲素与PTGS2以及雷公藤红素与PTGS2、CXCL8、STAT3有着很强的结合活性，雷公藤甲素和雷公藤红素可以抑制PTGS2和STAT3蛋白的表达。以上结果表明，雷公藤可能作用于这些靶点，通过调控细胞的增殖和凋亡，发挥抗炎、调节免疫的作用，从而抑制肝癌的恶化。

Study of the molecular mechanism of Tripterygium wilfordii inhibition of liver cancer based on network pharmacology and its preliminary verification

Based on the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP), the effective components of Tripterygium wilfordii against liver cancer have been screened. GeneCards, OMIM, Drugbank, GEO and other disease databases were used to screen differentially expressed genes, and the core substances and targets of mutual mapping were found. The pharmacodynamic component-target (C-T) network and protein interaction network (PPI) were constructed. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed to learn the biological mechanism, and molecular docking technology and biological experiments were used to verify it. The results showed that the main effective components of Tripterygium wilfordii are triptolide and celastrol. PTGS2, CXCL8, TGFB1, STAT3 and other core targets are mainly enriched in cancer and multiple inflammatory factor related pathways. Triptolide has strong binding activity with PTGS2, and celastrol has strong binding activity with PTGS2, CXCL8 and STAT3. Triptolide and celastrol can thus inhibit the expression of PTGS2 and STAT3 proteins. The above results show that Tripterygium wilfordii may act on these targets, and play an anti-inflammatory and immunoregulatory role by regulating cell proliferation and apoptosis, thereby inhibiting the progression of liver cancer.