Pachymic acid alleviates experimental pancreatic fibrosis through repressing NLRP3 inflammasome activation

Abstract

Pachymic acid (PA), a natural triterpenoid, possesses the capacity to repress inflammatory and profibrotic responses. However, the role of PA in pancreatic fibrosis remains unclear. Here the effect of PA on anti-fibrogenic response was investigated using in vivo and in vitro pancreatitis models. We demonstrated that PA treatment repressed TGF-β-induced pancreatic stellate cells (PSCs) activation in vitro, as evidenced by decreased expression of Collagen I, α-smooth muscle actin, and fibronectin. PA decreased Cerulein-induced acinar injury and pancreatic fibrosis in an experimental pancreatitis model. Mechanistically, PA repressed Cerulein or (TGF-β)-induced activation of nuclear factor (NF)-κB signaling and thus decreased NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome activation in PSCs. Pharmacological inhibition of NLRP3 repressed TGF-β-induced activation of PSCs. More important, NLRP3 activator partially attenuated the effect of PA on inhibiting PSCs activation. Collectively, these data demonstrate that PA represses PSCs activation and pancreatic fibrosis through repressing NF-κB/NLRP3 signaling.

Keywords: NF-κB; NLRP3; pachymic acid; pancreatic fibrosis; pancreatic stellate cells.