Effect of rosmarinic acid on oxidative damage in rats with acute pancreatitis based on the Nrf2/HO-1 signaling pathway

Objective:To investigate the effect of rosmarinic acid (RA) on oxidative damage in rats with acute pancreatitis (AP) based on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.Methods:A total of 40 rats were randomly divided into Sham group, AP group, RA group, and RA+ML385(Nrf2 inhibitor)group.The levels of serum amylase(AMY), lipase(LIP), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GSH-Px)levels were measured by enzyme-linked immunosorbent assay(ELISA).Histopathological changes in pancreatic tissue were assessed using HE staining.Cell apoptosis in pancreatic tissue was detected using TUNEL assay.Protein expression and mRNA expression of Nrf2 and HO-1 in pancreatic tissue were examined using western blotting and real-time fluorescence quantitative PCR (RT-qPCR), respectively.Results:Compared with the Sham group, the levels of AMY, LIP, IL-1β, IL-6, TNF-α, MDA, pancreatic index, pancreatic histopathological score and cell apoptosis rate in the AP group significantly increased, while the activities of SOD, levels of GSH-Px, and protein and mRNA expression of Nrf2 and HO-1 in pancreatic tissue significantly decreased (P< 0.05).Compared with the AP group, the levels of AMY, LIP, IL-1β, IL-6, TNF-α, MDA, pancreatic index, pancreatic histopathological score, and cell apoptosis rate in the RA group decreased, while the activities of SOD, levels of GSH-Px, and protein and mRNA expression of Nrf2 and HO-1 in pancreatic tissue significantly increased(all P< 0.05).The RA+ML385 group showed higher levels of AMY, LIP, IL-1β, IL-6, TNF-α, MDA, pancreatic index, pancreatic histopathological score, and cell apoptosis rate compared with the RA group, while the activities of SOD, levels of GSH-Px, and protein and mRNA expression of Nrf2 and HO-1 in pancreatic tissue were lower than those in the RA group (all P< 0.05).Conclusion:RA can inhibit inflammation and oxidative damage in AP rats and alleviate pancreatic tissue pathological damage.Its mechanism of action may be related to the activation of the Nrf2/HO-1 signaling pathway.