Network Pharmacology Analysis to Explore the Pharmacological Mechanism of Effective Chinese Medicines in Treating Metastatic Colorectal Cancer using Meta-Analysis Approach

The role of traditional Chinese medicine (TCM) on treatment of metastatic colorectal cancer (mCRC) remains controversial, and its active components and potential targets are still unclear. This study mainly aimed to assess the efficacy and safety of TCM in mCRC treatment through meta-analysis and explore the effective components and potential targets based on the network pharmacology method. We systematically searched PubMed, EMBASE, Cochrane, CBM, WanFang, and CNKI database for randomized controlled trials (RCTs) comparing the treatment of mCRC patients with and without TCM. A meta-analysis using RevMan 5.4 was conducted. In total, 25 clinical trials were analyzed, and the result demonstrated that TCM was closely correlated with the improved OS (HR: 0.63; 95% CI: 0.52-0.76; [Formula: see text] < 0.00001) and PFS (HR: 0.73; 95% CI: 0.61-0.88; [Formula: see text] = 0.0010). Then, high-frequency Chinese herbs from the prescriptions extracted from the trails included in the OS meta-analysis were counted to construct a core-effective prescription. The TCMSP database was used to retrieve the active chemical components and predict herb targets. The Genecards, OMIM, Disgenet, DrugBank, and TTD database were searched for colorectal cancer targets. R-package was used to construct the Component-Target (C-T) network based on the intersection genes. Further, we extracted hub genes from C-T network and performed functional enrichment and pathway analysis. Finally, the C-T network showed 120 herb and disease co-target genes, and the most important top 10 active components were: Quercetin, Luteolin, Wogonin, Kaempferol, Nobiletin, Baicalein, Licochalcone A, Naringenin, Isorhamnetin, and Acacetin. The first 20 hub genes were extracted: CDKN1A, CDK1, CDK2, E2F1, CDK4, PCNA, RB1, CCNA2, MAPK3, CCND1, CCNB1, JUN, MAPK1, RELA, FOS, MAPK8, STAT3, MAPK14, NR3C1, and MYC. Thus, effective Chinese herb components may inhibit the mCRC by targeting multiple biological processes of the above hub genes.