Pentyl (2E)-3-(3-methoxyphenyl) prop-2-enoate attenuates acute respiratory syndrome induced by intestinal ischemia and reperfusion in rats

Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory condition characterized by high morbidity and mortality, with limited effective pharmacological therapies currently available. The search for novel compounds with anti-inflammatory and antioxidant properties remains essential to improve clinical outcomes. In this context, Pentyl (2E)-3-(3-methoxyphenyl)prop-2-enoate (MAP), a phenolic cinnamic acid derivative, emerges as a promising candidate due to its potential biological activities. This study aimed to investigate the anti-inflammatory effects of MAP using an integrative approach combining in silico and in vivo analyses. Initially, pharmacokinetic and toxicological predictions indicated favorable oral bioavailability, adequate distribution, low predicted toxicity, and compliance with Lipinski's rules. Molecular docking studies demonstrated significant interactions with key inflammation-related targets, while density functional theory (DFT) calculations revealed electronic stability and favorable orbital distribution. Additionally, molecular dynamics simulations confirmed the stability of ligand-protein complexes, with low root mean square deviation (RMSD) values over time. Subsequently, the in vivo effects of MAP were evaluated in a rat model of intestinal ischemia-reperfusion (iI/R)-induced ARDS. Oral administration of MAP (20, 40, or 60 mg/kg) significantly reduced leukocyte infiltration, oxidative stress markers, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) while attenuating histopathological lung damage. Furthermore, MAP enhanced antioxidant defenses by increasing glutathione levels and catalase activity, alongside reducing nitric oxide production. Importantly, no evidence of acute genotoxicity was observed at the tested doses. In summary, MAP demonstrated consistent anti-inflammatory and antioxidant effects across computational and experimental models, effectively mitigating key pathological features of ARDS. These findings suggest that MAP is a promising adjuvant therapeutic candidate for acute respiratory inflammatory conditions, although further studies are necessary to elucidate its mechanisms of action and support its potential clinical application.