Kaempferol protects rats with severe acute pancreatitis through regulating NF-κB and Keap1–Nrf2 signaling pathway

Abstract

Kaempferol (KF) is an important natural anti-inflammatory flavonol. Acute pancreatitis (AP) is an inflammatory disorder, which in about 20% cases may develop into severe acute pancreatitis (SAP) with a high mortality rate. This research was to study the effects and mechanism of kaempferol on SAP. SAP was induced by sodium taurocholate. The level of cytokines was analyzed by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) and Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2 (Keap1–Nrf2) proteins was analyzed by Western blot assay. Pathological changes in the pancreas were evaluated by hematoxylin and eosin staining. Kaempferol attenuated pancreatic injury in SAP rats, including reduction in inflammatory infiltration and necrosis. The level of serum amylase and lipase was also decreased in kaempferol-treated SAP rats. Kaempferol inhibited the expression of inflammatory mediators (nuclear factor-α, Interlukin-1β, and Interlukin-6), and alleviated the oxidative stress characterized by the decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) levels. Kaempferol decreased the expression of cleaved caspase 3 and anti-apoptotic protein Bcl-2, which indicated that kaempferol could inhibit apoptosis of pancreatic cells in SAP rats. Kaempferol treatment could decrease the expression of p-p65 and the amount of nuclear Nrf2 (Nu-Nrf2), which demonstrated that kaempferol inhibited the NF-κB activation and enhanced the Keap1–Nrf2 pathway. Our research indicated that kaempferol could attenuate the pancreatic injury of SAP by regulating NF-κB and Keap1–Nrf2 signaling pathway. Kaempferol could serve as a natural candidate for treating SAP.