Catechin hydrate ameliorates cerulein‑induced chronic pancreatitis via the inactivation of TGF‑β/Smad2 signaling

Chronic pancreatitis (CP) is a pancreatic inflammatory disease associated with histological changes, including fibrosis, acinar cell loss and immune cell infiltration, and leads to damage of the pancreas, which results in pain, weight loss and loss of pancreas function. Catechin or catechin hydrate (CH) has antioxidant, anticancer and immune-regulatory effects. However, unlike other catechins, the antifibrotic effects of (+)-CH have not been widely studied in many diseases, including CP. Therefore, the anti-fibrotic effects of (+)-CH against CP were evaluated in the present study. To assess the prophylactic effects of CH, (+)-CH (1, 5 or 10 mg/kg) or ethanol was administered 1 h before first cerulein (50 µg/kg) injection. To assess the therapeutic effects, (+)-CH (5 mg/kg) or ethanol was administered after cerulein injection for one or two weeks. In both methods, cerulein was injected intraperitoneally into mice once every hour, six times a day, four times a week, for a total of three weeks, to induce CP. The data showed that (+)-CH markedly inhibited glandular destruction and inflammation during CP. Moreover, (+)-CH prevented pancreatic stellate cell (PSC) activation and the production of extracellular matrix components, such as fibronectin 1 and collagens, which suggested that it may act as a novel therapeutic agent. Furthermore, the mechanism and effectiveness of (+)-CH on pancreatic fibrosis were investigated in isolated PSCs. (+)-CH suppressed the activation of Smad2 and fibrosis factors that act through transforming growth factor-β (TGF-β) or platelet-derived growth factor. These findings suggest that (+)-CH exhibits antifibrotic effects in cerulein-induced CP by inactivating TGF-β/Smad2 signaling.