Pectin-loaded ferulic acid nanoparticles: A potential therapeutic strategy for ulcerative colitis via modulation of the cGAS-STING pathway

Abstract

Ulcerative colitis (UC) is a persistent intestinal disorder featuring periodic flare-ups of the colon's inner lining inflammation. Current therapeutic strategies, while effective in managing symptoms, are often limited by side effects and high costs. This study investigates the potential of pectin-loaded ferulic acid (PC-FA) nanoparticles as a novel therapeutic approach for UC, focusing on their ability to modulate the cGAS-STING pathway, a key mediator in the inflammation associated with UC. PC-FA nanoparticles were prepared and characterized for their physicochemical properties, antioxidant capacity, biocompatibility, and influence on the cGAS-STING pathway. In vitro experiments demonstrated that PC-FA nanoparticles enhanced the solubility and bioavailability of ferulic acid (FA), reduced oxidative stress, and protected colon epithelial cells from damage caused by the administration of dextran sulfate sodium (DSS). In vivo studies in a DSS-induced colitis mouse model showed that PC-FA nanoparticles mitigated weight reduction, lowered disease activity index (DAI) scores, and sustained colon length, and ameliorated histopathological changes. Additionally, PC-FA nanoparticles effectively targeted DNA damage and inhibited the cGAS-STING pathway, leading to a significant reduction in pro-inflammatory cytokines. Pharmacokinetic studies revealed rapid absorption of PC-FA in the bloodstream, with a predominant distribution in the intestines. The study concludes that PC-FA nanoparticles are a promising therapeutic strategy for UC, offering targeted drug delivery, enhanced bioavailability, and anti-inflammatory effects.