Methanol Extract from Ranunculus repens L. Down-Regulated Galectins 4 and 9, and Mitigated Chronic Pancreatitis in an Experimental Rat Model

Abstract

Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease in which oxidative stress (OS) promotes pancreatic stellate cells activation and fibrosis. <i>Ranunculus repens</i> L. (<i>R. repens</i>) has been used in Algerian traditional medicine to treat conditions like hepatitis and diabetes. Galectins are β-galactoside-binding lectins implicated in several pathological processes, including inflammation. This study aimed to analyse the chemical composition and evaluate the protective effects of <i>R. repens</i> methanol extract (RRME) in an experimental CP model, as well as in cultured pancreatic cells. CP was induced by intraperitoneal injections of L-arginine in rats. The pancreas was examined histopathologically, using hematoxylin and eosin, and picrosirius red staining. OS markers were assessed in pancreatic homogenates, and RT-qPCR analysis was performed to evaluate the expression of fibrosis markers, proinflammatory cytokines, and galectins 4 and 9. The extract was characterized by Ultra-performance liquid chromatography mass spectrometry, and its antioxidant and antiapoptotic activities were evaluated in vitro using H₂O₂-induced intracellular reactive oxygen species (ROS) generation and paclitaxel-induced apoptosis in pancreatic cell lines. The results showed that treatment with RRME improved relative pancreatic weight and lowered serum lipase activities. It mitigated oxidative stress in pancreatic tissues and reduced fibrosis levels. Inflammation was attenuated, as indicated by decreased interleukin-6, tumor necrosis factor alpha, and leukocyte infiltration. Moreover, RRME down-regulated galectins 4 and 9. Finally, RRME attenuated ROS generation and apoptosis in vitro. These findings suggested that RRME may have therapeutic potential against CP by modulating OS and fibrosis.