A preliminary study on Fructus Aurantii extract against hepatocarcinoma via glycolysis and PD-1/PD-L1 pathway

Abstract

Fructus Aurantii (FA) is a traditional herbal medicine that has been widely used for thousands of years in China and possesses a variety of pharmacological effects. FA is full of flavonoids. Several natural bioactive compounds of FA are involved in the treatment of various types of cancers, however, the beneficial effects of FA in hepatocarcinoma and the potential mechanisms of its therapeutic effects have not been fully explored. The present study investigates the anticancer role of flavonoids extracted from FA on human hepatoblastoma cell, HepG2. Eriocitrin, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, hesperitin, poncirin, meranzin, nobiletin and tangeretin were identified in FAE. The FAE inhibit the proliferation of HepG2 cells in a dose-dependent manner. Metabolic alteration was detected by cell metabolomics and quantitative real time polymerase chain reaction. Flavonoids decreased the level of glycolysis rate-limiting enzymes gene expression in HepG2 cells. It was also observed that the PD-1 and PD-L1 gene expression level were decreased in FAE-treated cells. Collectively, these results suggest that flavonoid extracted from FA inhibits HepG2 cell proliferation by glycolysis and its downstream of PD-1/PD-L1 pathway. These findings suggest that the possible mechanism by which FA exerts its activities in the treatment of hepatocarcinoma and lays a foundation for further experiments and the development of a rational clinical application of FA, which still needs further in vivo investigation in animals and human beings.