Galangin protects against acute pancreatitis by inhibiting ROS-induced acinar cell apoptosis and M1-type macrophage polarization

Acute pancreatitis (AP) is a common disease in the digestive tract and is characterized by elevated serum pancreatic proteases and abdominal pain. AP, especially severe AP, is still a deadly disease; thus, identifying potential therapies and exploring the underlying mechanism are essential for AP patients. Galangin, a flavonoid extracted from traditional medicinal herbs, shows robust anti-inflammatory and cell protection abilities in various diseases, but its role in AP has not been unveiled. We explored the function and mechanism of galangin in AP using caerulein-induced mouse, isolated acinar cell and bone marrow-derived macrophage models. The pancreas was analyzed using histology and immunofluorescent staining; cytokine levels, the activity of amylase and lipase, and reactive oxygen species (ROS) levels were determined; infiltrating macrophages were analyzed by flow cytometry; certain proteins and RNAs were analyzed; and the safety of galangin was also evaluated. We found that galangin significantly attenuated AP in mice and acinar cells by decreasing ROS and apoptosis via the promotion of Srxn1 expression through an NRF2-dependent pathway. Galangin significantly reduced the number of infiltrating macrophages and inhibited the activation of M1-type macrophages by negatively regulating NF-κB signaling. Compared to the control, no obvious side effects were observed in the galangin-treated group. Thus, our study demonstrated that galangin is a safe and efficient drug to treat AP by preventing injury to acinar cells and inhibiting M1-type macrophages, suggesting a potential therapy for AP in the future. • Galangin protects against acute pancreatitis in isolated acinar cells and mice. • Reactive oxygen species and apoptosis are decreased by galangin in acinar cells. • NRF2/SRXN1 is responsible for the protection effect of galangin in acinar cells. • Galangin inhibits acute pancreatitis-induced activation of M1-type macrophages by NF-κB signaling.