Intestinal anti-inflammatory, histopathologic and anti-oxidative regulatory effects of total alkaloids extract from Linum usitatissimum L. (flaxseed) in vivo

Ethnopharmacological relevance: Linum usitatissimum L., commonly known as flaxseed, is a perennial herb in the Lineaceae family that has been traditionally used to manage gastrointestinal disorders and diarrhea. The health benefits and medicinal applications of flaxseed can be attributed to the presence of some beneficial compounds, such as omega-3 fatty acids, tocopherol, cyclic peptides, alkaloids, mucilage, and phenylpropanoids. Aim of the study: This investigation explored the potential anti-inflammatory and antioxidant properties of the total alkaloid extract of Linum usitatissimum L. seeds (ALU) in a model of Crohn’s disease induced by 2,4-dinitrobenzenesulfonic acid (DNBS) in BALB/c mice. Materials and methods: ALU fraction was chemically characterized by liquid chromatography combined with electrospray ionization mass spectrometry (LC-ESI-MS/MS). Six groups of mice (n = 6) were divided as follow: healthy group, colitic control, Dexamethasone treated-group (2.4 mg/kg) and three group for ALU treatment (50, 100 and 200 mg/kg). Intrarectal instillation of DNBS (250 mg/kg) induced colonic inflammation accompanied by body weight loss, colonic architecture modification, inflammatory cells infiltration and excessive inflammatory markers production. Tissues sample were used to assess the histological damages and eventual goblet cells loss (H & E and PAS staining) and to evaluate inflammatory and oxidative statute (MPO, NO, H₂O₂, MDA, CAT and GSH). Results: The phytochemical analysis of total alkaloid fraction of LU revealed the presence of 10 compounds. Oral administration of ALU (50, 100, and 200 mg/kg) significantly ameliorated DNBS-induced colitis in mice in a dose-dependent manner. ALU treatment mitigated body weight loss, reduced the weight/length (W/L) ratio, and improved clinical outcomes, including diarrhea and food intake. Histological analyses revealed that ALU treatment, preserved colonic architecture, enhanced goblet cell numbers, reduced neutrophil infiltration, and minimised mucosal damage, with a comparable effect to dexamethasone treatment. ALU also promoted mucosal healing and neutral mucin retention. Furthermore, ALU exerted potent anti-inflammatory and antioxidant effects by modulating key markers such as MPO, NO, H₂O₂, MDA, CAT, and GSH, supporting its protective role against colonic inflammation. Conclusion: These findings indicate that alkaloid fraction extracted from Linum usitatissimum L. have strong anti-inflammatory and antioxidant properties in a DNBS-induced colitis model in BALB/c mice.