Modulation of inflammatory and oxidative stress pathways by ethanolic extract of Suaeda fruticosa Forssk. Ex J.F.Gmel in animal models of ulcerative colitis.

Chronic inflammation accompanied by oxidative imbalance plays an essential role in the pathogenesis of ulcerative colitis (UC). Suaeda fruticosa has well-established antioxidant, cytoprotective and anti-inflammatory properties. This study evaluated the efficacy of the 80% ethanolic extract of S. fruticosa and its primary phytoconstituents in experimental models of UC. Ethanolic extract of Suaeda fruticosa (SF-Et) prepared by maceration was characterised by quantitative (TPC, TFC, TTC, and TSC) and GC-MS techniques. The nitrite scavenging assay was performed to determine the reactive nitrogen species (RNS) scavenging property. 5% dextran sulfate sodium (DSS, 40KDa Mw) and 3% acetic acid (2 mL) solutions were used to induce UC in rats. Animals were treated with 125, 250, and 500 mg/kg of SF-Et, 500 mg/kg of sulfasalazine, and 10 mg/kg of the compound combination (CC). Physical parameters, such as body weight, stool consistency, and rectal bleeding were examined to determine the severity of UC. Histopathological observations of colon tissues, haematological testing, and qPCR analysis of inflammatory genes were performed to establish the in vivo efficacy of SF-Et. Additionally, the MTT assay was used to evaluate the cytotoxicity of SF-Et and its components against HCT 116 colorectal cancer cells. ADMET predictions for selected compounds were performed using online tools. Quantitative phytochemical screening confirmed the presence of 69.49 ± 6.27 mg GAE/g of TPC, 353.01 ± 8.05 mg QE/g of TFC, 21.7% of TSC, and 34.26 ± 2.02 mg TAE/gram of TTC in SF-Et. GC-MS analysis confirmed the presence of farnesol, n-hexadecanoic acid, and thymol  (previous data). Nitrite scavenging activity confirmed the moderate RNS scavenging potential of SF-Et. In DSS and acetic acid-induced colitis models, oral administration of 500 mg/kg of SF-Et and 10 mg/kg of the compound combination significantly mitigated colitis signs, restored haematological parameters, and protected the architecture of colon tissues. qPCR analysis revealed significant (p < 0.05) down-regulation in mRNA expression of inflammatory markers (TNF-α, IL-1β, IL-6, iNOS, COX-2, NF-κB, and PGE2) and up-regulation of the anti-inflammatory cytokine, IL-10, in the SF-Et, CC and SSZ administered groups. Treatment with SF-Et and SSZ produced significant (p < 0.05) elevation in serum GSH and reduction in nitric oxide levels than diseased control group. Moreover, SF-Et and the CC treatment showed dose-dependent cytotoxicity against HCT 116 cells. ADMET prediction showed good intestinal absorption (> 90%) and a relatively low toxicity profile of studied compounds. These findings confirm that S. fruticosa and its major compounds can mitigate UC development by modulating inflammatory and oxidative stress biomarkers.