Avaliação da atividade citotóxica, gastroprotetora e anti-inflamatória da emulsão do óleo da semente de Euterpe oleracea Mart. em modelos in vitro e in vivo

Abstract

Gastrointestinal diseases are a significant concern for global health, negatively impacting quality of life and requiring new effective treatments. Euterpe oleracea Mart. (açaí) is an Amazonian palm whose fixed seed oil, a little-explored byproduct of the species, contains bioactive fatty acids with pharmacological potential in various diseases. Although E. oleracea is widely studied, there are still gaps in knowledge about its potential in the treatment of gastrointestinal disorders. This work aimed to evaluate the cytotoxic, gastroprotective, and anti-inflammatory activity of the E. oleracea seed oil emulsion (EOR) in in vitro and in vivo experimental models. Material and methods: E. oleracea fruits were collected in the municipality of São Luís, MA. After depulping, the seeds were ground in a knife mill to obtain flour, which was then subjected to oil extraction using the Soxhlet method. The fatty acid profile was identified by Gas Chromatography coupled to Mass Spectrometry (GC-MS). The emulsion (EOR) was prepared with the extracted oil, surfactant compound Tween 80 (8%), and distilled water. Cytotoxicity was evaluated in murine macrophages (RAW 264.7) using the MTT colorimetric assay with concentrations of 62.5, 125, 250, 500, and 1000 µg/mL. In in vivo assays, the gastroprotective potential was determined using the acidified ethanol gastric ulcer (GU) induction model, and the anti-inflammatory potential was determined using the TNBS-induced ulcerative colitis (UC) model, both in Mus musculus Swiss mice. The EOR emulsion was administered orally at doses of 100, 300, 600, and 1000 mg/kg, and the positive control consisted of the drugs Omeprazole 40 mg/kg and Dexamethasone 4 mg. The analyses performed demonstrated that the açaí seed oil emulsion (EOR), whose lipid profile is dominated by oleic (23.55%), myristic (23.51%), linoleic (21.22%), and palmitic (17.69%) acids, exerts a gastroprotective and anti-inflammatory action in murine models of acute gastric lesion (ethanol/HCl) and colitis (TNBS). In gastric ulcer, EOR 300–600 mg/kg markedly reduced the lesion (ILU 57.6% lower), preserved mucosal architecture, and increased mucus production, with performance comparable to or superior to the positive control. In colitis, a consistent gradient of histological protection was observed, with EOR 300 and 600 mg/kg reaching grade 0 colitis, equivalent to dexamethasone, and accompanied by an increase in GSH and a decrease in MPO levels, indicating less oxidative stress and neutrophilic infiltrate. In parallel, EOR proved to be non-cytotoxic to RAW 264.7 macrophages in the range of 62.5–250 μg/mL (24–48h), supporting a cellular safety profile compatible with biotherapeutic use. Notably, at an intermediate dose (300 mg/kg), a regulatory signal with increased plasma IL-10 was observed, suggesting an additional anti-inflammatory mechanism. The set of findings supports the hypothesis that EOR acts on multiple defense axes in the mucosa—muco-bicarbonate barrier, attenuation of oxidative stress, and containment of neutrophilia—resulting in gastric cytoprotection and resolution of colonic inflammation. In addition to the biomedical impact, the study adds value to an agro-industrial residue, aligning sustainability and innovation. In summary, EOR combines tissue efficacy, mechanistic coherence, and a safety signal, establishing itself as a promising platform for the development of phytotherapeutic/nutraceutical products aimed at gastrointestinal disorders. Future studies should refine dosage and formulation, characterize cytokine kinetics/compartmentalization, and validate mechanisms to advance preclinical translation.