Curcumin ameliorates cerulein‑induced chronic pancreatitis through Nrf‑2/HO‑1 signaling.

Abstract

Chronic pancreatitis (CP) is an invasive inflammatory disorder characterized by endocrine and exocrine dysfunction. There are currently no effective drugs for the treatment of CP. The present study investigated whether curcumin improves cerulein‑induced CP fibrosis in a mouse model and pancreatic stellate cells (PSCs). The CP mouse model was established by intraperitoneally injecting cerulein (50 µg/kg) for 3 weeks (six times at 1 h intervals/day; 4 days/week). To investigate the effects of curcumin, dimethyl sulfoxide or curcumin was injected intraperitoneally 1 h before the first daily injection of cerulein. To determine the severity of CP, the pancreas was harvested 24 h after the last cerulein injection for histological examination and assessment of PSC activation and collagen deposition. Additionally, levels of the nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) were evaluated to determine the mechanism underlying the anti‑fibrotic effect of curcumin in PSCs. Curcumin improved pancreatic injury associated with CP by inhibiting PSC activation and collagen deposition. Moreover, curcumin increased HO‑1 expression levels via the activation of Nrf2 in PSCs, which suppressed the activation of PSCs. In conclusion, the present results suggest that curcumin can ameliorate pancreatic fibrosis induced by repetitive cerulein challenges via the induction of HO‑1 and is a beneficial agent for the treatment of CP.