Abstract
As a natural compound present in a variety of plants, hispidulin has an inhibitory effect on tumors. In this study, we combined network pharmacology, bioinformatics methods and experimental verification to explore the potential targets of hispidulin in inhibiting hepatocellular carcinoma. 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 and in vivo studies, hispidulin inhibited the growth of hepatocellular carcinoma, induced apoptosis and inhibited migration of hepatocellular carcinoma cells and exhibited no significant toxicity to the normal tissues and organs of mice. It downregulated the expression of CDK1, CCNB1, SRC, AURKB protein and attenuated the PI3K/AKT pathway signal. These results suggest that hispidulin can exert anti-HCC effects through the PI3K/AKT pathway. Hispidulin can inhibit the occurrence and progression of hepatocellular carcinoma through multiple targets, showing good anti-tumor efficacy in vitro and in vivo, and has the potential to develop new therapeutic drugs for hepatocellular carcinoma.