Effective components of Coptidis Rhizoma and Cinnamomi Cortex in the treatment of renal cell carcinoma and their mechanism of action

This study aimed to investigate the mechanism of the Coptidis Rhizoma and Cinnamomi Cortex (HL-RG) drug pair in the intervention of renal cell carcinoma (RCC) using network pharmacology, molecular docking, and cell experiments. Network pharmacology analysis predicted 42 active components in HL-RG and identified 227 potential targets. Among these, 50 targets were specifically associated with RCC, and 18 were identified as hub genes. Three components (quercetin, oleic acid, tetrandrine) were highlighted as particularly effective. The results of the gene ontology (GO) annotation showed that HL-RG may treat RCC by regulating biological processes such as inflammation, immune response, cell cycle process, and lipid metabolism. Kyoto Gene and Genome Encyclopedia (KEGG) enrichment revealed that the key targets of HL-RG in treating RCC were enriched in the proteoglycans in cancer, and the HIF-1 signaling pathway. Molecular docking results demonstrated that 87% of the interactions exhibited binding energies stronger than −5.0 kcal/mol, indicating favorable binding affinity between the core active components and key targets. Experimental validation using quantitative real-time polymerase chain reaction and Western blot in 786-O cells demonstrated that tetrandrine (TET) and quercetin (QUE) downregulated the mRNA and protein levels of G1/S-specific cyclin-D1 (CCND1) and Transforming growth factor beta-1 (TGFB1), and upregulated the mRNA levels of Catalase (CAT). Additionally, QUE downregulated the mRNA levels of Receptor tyrosine-protein kinase erbB-2 (ERBB2) and upregulated the mRNA levels of Pro-epidermal growth factor (EGF). Furthermore, oleic acid (OA), TET, and QUE downregulated the protein levels of Matrix metalloproteinase-9 (MMP9). In conclusion, the therapeutic effect of the HL-RG combination against RCC is primarily mediated by its bioactive components, QUE, OA, and TET. These components regulate the HIF-1 signaling pathway, activating genes involved in the cellular response to hypoxia and modulating the expression of proteins that control glucose metabolism, cell proliferation, and angiogenesis.