Identification of peanut skin components for treating hepatocellular carcinoma via network pharmacology and in vitro experiments

Peanut skin (PS) contains various flavonoids and phenols that have antitumor and antioxidant effects. However, no research has been conducted on PS and hepatocellular carcinoma (HCC). Therefore, this study sought to explore the potential mechanism of PS in treating HCC. PS was searched for in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SYMMAP databases. HCC targets were searched for in five major databases. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking and molecular dynamics simulation were used for verification. Furthermore, in vitro experiments were used to verify the regulation of PS on human HCC (HepG2) cells. Ten ingredients and 95 common targets were identified for PS and HCC, respectively. The key targets of ingredients mainly relate to pathways such as hepatitis B, lipid and atherosclerosis, advanced glycation end products (AGEs)-AGE receptors (RAGEs) signaling pathway in diabetic complications, interleukin-17 (IL-17) signaling pathway, mitogen activated kinase-like protein (MAPK) signaling pathway, the PI3K-Akt signaling pathway. In addition, the molecular docking and molecular dynamics simulation analysis indicated the ingredients had strong binding ability with the targets. Moreover, in vitro experiments confirmed that luteolin can promote the apoptosis of HepG2 cells by controlling the expression of phosphorylated protein-tyrosine kinase (p-AKT). This study provides preliminary evidence that PS produces a marked effect in regulating multiple signaling pathways in HCC through multiple ingredients acting on multiple core genes, including AKT serine/threonine kinase 1 (AKT1), MYC, caspase 3 (CASP3), estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), jun proto-oncogene(JUN), and provides the basis for follow-up research to verify the mechanism of action of PS in treating HCC. In this study, PS was searched through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SYMMAP database. Then search for HCC targets in the five major databases. Next, we created a network and performed Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, molecular docking and molecular dynamics simulation were used for verification. Finally, cell experiments were used to verify the regulation of PS on human hepatocellular carcinoma (HepG2) cells. The results displayed ten ingredients and 95 common targets are identified for PS and HCC. And, it preliminarily showed that in the treatment of HCC, PS produces a marked effect in regulating multiple signaling pathways through multiple ingredients acting on multiple core genes, such as AKT1, MYC, CASP3, ESR1, EGFR, JUN, and provides the basis for follow-up research to verify the mechanism of action of PS in treating HCC.image