Mechanistic insights and therapeutic potential of hispidulin in hepatocellular carcinoma: a bioinformatics and experimental study

Background: As a natural compound present in a variety of plants, hispidulin has an inhibitory effect on tumors. Methods: In this study, we combined network pharmacology, bioinformatics methods and experimental verification to explore the potential targets of hispidulin in inhibiting hepatocellular carcinoma. Results: The network pharmacology analysis showed that the pharmacokinetic properties of hispidulin conformed to the Lipinski's five rules, and it had no hepatotoxicity, carcinogenicity, cytotoxicity, immunotoxicity, mutagenicity, and had the potential to be developed as a drug. The results of network pharmacology and bioinformatics analysis showed that hispidulin may interfere with the occurrence and progression of hepatocellular carcinoma by affecting CDK1, SRC, CCNB1, AURKB and PI3K-AKT signaling pathways. In vitro, hispidulin can inhibit the growth of hepatocellular carcinoma, induce apoptosis and inhibit migration of hepatocellular carcinoma cells. Down-regulate the expression of CDK1, CCNB1, SRC, AURKB protein and weaken the PI3K-AKT pathway signal. It has no obvious toxicity to normal liver cells. Conclusions: Hispidin can inhibit the occurrence and progression of hepatocellular carcinoma through multiple targets, showing good anti-tumor efficacy in vitro, and has the potential to develop new therapeutic drugs for hepatocellular carcinoma.