Apigenin alleviated PA-induced pyroptosis by activating autophagy in hepatocytes.

Abstract

Apigenin is a kind of natural flavonoid that abundantly exists in fruits and vegetables. Pyroptosis is a new, pro-inflammatory type of programmed necrosis cell death, and the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the key molecule to induce pyroptosis. Excessive hepatic pyroptosis results in liver injury. In the study, we found for the first time that apigenin could alleviate palmitic acid (PA)-induced NLRP3 inflammasome activation and pyroptosis in HepG2 cells and primary mouse hepatic cells. Meanwhile, apigenin could promote the autophagy of hepatocytes. When the autophagy inhibitor chloroquine (CQ) was added, the data showed that the recovery effect of apigenin on PA-induced pyroptosis was weakened, indicating that apigenin could alleviate PA-induced pyroptosis by activating autophagy. Further mechanistic studies showed that apigenin regulated the NLRP3 inflammasome through two ways, so as to alleviate PA-induced pyroptosis. On the one hand, apigenin eliminated damaged mitochondria by activating autophagy, thereby clearing reactive oxygen species (ROS) production and inhibiting the activation of the NLRP3 inflammasome, and on the other hand, activation of autophagy could directly degrade the NLRP3 inflammasome. Our study provides a new idea and target for the use of functional factors in food to alleviate liver injury.