Sinapic Acid Alleviates Acute Pancreatitis in Association with Attenuation of Inflammation, Pyroptosis, and the AMPK/NF-[Formula: see text]B Signaling Pathway.

Abstract

Among the diseases of the digestive system, the incidence of acute pancreatitis (AP) has increased. Although the AP is primarily self-limited, mortality remains high when it progressed to severe acute pancreatitis (SAP). Despite significant advances in new drug development, treatments for AP are not ideal. Here, we discovered a novel hydroxycinnamic acid, sinapic acid (SA), which is widely distributed in plants and is an effective treatment for AP. Using in vitro and in vivo models, we demonstrated that pretreatment with SA ameliorated cerulein-induced pancreatic damage and inflammation and inhibited the activation of Caspase-1 and Caspase-11, which mediate pyroptosis of pancreatic acinar cells during AP. These effects may occur through the inhibition of AMPK phosphorylation and downregulation of NF-[Formula: see text]B. Our findings demonstrate the therapeutic effects and reveal the underlying mechanisms of SA, which warrants its further study as an effective treatment for AP.