Understanding the anti-hepatocarcinogenic activity of typical flavonoids from Citri Reticulatae pericarpium and their mechanism via HepG2 cells apoptosis experiment and molecular docking

Citri Reticulatae Pericarpium (CRP) has attracted much attention due to its abundant flavonoids, while their antitumor activity has not been sufficiently studied. Effects of CRP flavonoids on the proliferation, apoptosis, and migration of hepatocellular carcinoma cells (HepG2) were investigated by assessing cell activity, cell migration, cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential, and cell cycle. Results indicated that 3 purified flavonoids, including hesperidin, nobiletin, and tangeretin, significantly inhibited HepG2 cell activity and migration, promoted ROS production, decreased mitochondrial membrane potential, and arrested the cell cycle at the G2/M and S phases. These compounds also induced apoptosis by upregulating pro-apoptotic proteins (Bax, Caspase 9, Caspase 3, Cytochrome C) and downregulating anti-apoptotic factors (Bcl-2, PARP). Molecular docking revealed strong binding affinities between these flavonoids and the proteins Bax and Bcl-2. Results provide new perspectives for utilization of active ingredients from CRP with anti-hepatocellular carcinoma characteristics and understanding their underlying mechanisms.