Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO‐1 Pathway

Abstract

Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.

Tanshinone IIA Protects against Acute Pancreatitis in Mice by Inhibiting Oxidative Stress via the Nrf2/ROS Pathway

“…Studies have indicated that oxidative stress and the related production of reactive oxygen species (ROS) play a major role in pancreatic acinar cell injury in AP [12,13]. Moreover, many studies suggest that antioxidant treatment can effectively reduce pancreatic tissue damage and inflammatory response in mice of AP, such as carbon monoxide-bound hemoglobin vesicle [14], coenzyme Q10 [15], and isoliquiritigenin we reported earlier [16]. However, it is far away from the clinical application.…”

“…injection of caerulein (200 μg/kg, 10 times at one-hour intervals; Cat. Pep03263, Nanjing Peptide Co. Ltd., Nanjing, China) [16,17]. Mice were randomized into five groups: vehicle, caerulein, caerulein+low-dose TSA (5 mg/kg), caerulein+ medium-dose TSA (25 mg/kg), and caerulein+high-dose TSA (50 mg/kg).…”

“…injection of L-Arg (4 g/kg, 2 times at a 1 h interval; Cat. A5006, Sigma-Aldrich, St. Louis, MO, USA) [16], mice were also randomized into three groups: vehicle, L-Arg, and L-Arg+TSA. After the first injection of L-Arg, a medium dose of TSA (25 mg/kg) was injected intraperitoneally at 24 h and 48 h. All mice were sacrificed 72 h after L-Arg administration.…”

“…KGT004 and KGT006, Nanjing KeyGen Biotech Co. Ltd., Nanjing, China). The ROS generation in pancreatic tissues was detected by fluorescent probe-Dihydroethidium (DHE), and the detailed procedures were reported in our previous study [16].…”

“…Blotting. Referring to our previous methods [16], primary antibodies against Nrf2 (1 : 1000 dilution; Cat. ab31163, Abcam, Cambridge, UK), heme oxygenase (HO-1) (1 : 1000 dilution; Cat.…”