Aloe vera Water Extract (AVWE) Protects Intestinal Epithelial Barrier Integrity by Attenuating Oxidative Stress and Inflammatory Responses

Oxidative stress, excessive inflammatory signaling, and disruption of the intestinal epithelial barrier are pathological features associated with inflammatory bowel disease (IBD) pathogenesis. These pathological processes have prompted interest in natural products that may help limit oxidative stress and inflammation. Although Aloe vera has demonstrated antioxidant and anti‐inflammatory activity, its capacity to preserve intestinal epithelial barrier integrity under inflammatory conditions remains insufficiently characterized. Accordingly, the potential protective effects of Aloe vera water extract (AVWE) against oxidative stress, inflammatory responses, and epithelial barrier disruption were investigated. The antioxidant potential of AVWE was evaluated by quantifying its total phenolic and flavonoid contents and measuring its capacity to scavenge radicals. Cellular oxidative stress, inflammatory responses, and epithelial barrier integrity were subsequently evaluated through a DCF‐DA assay, protein and gene expression analyses, immunofluorescence staining, transepithelial electrical resistance (TEER), and permeability assays. In addition, phytochemical constituents were tentatively identified using ultraperformance liquid chromatography–quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐QTOF‐MS/MS), followed by molecular docking analysis of the identified compounds against NF‐κB. AVWE demonstrated potent free radical scavenging activity and significantly suppressed intracellular ROS generation induced by IL‐6. AVWE also attenuated the activation of inflammation‐related signaling pathways, with a concurrent decrease in downstream inflammatory mediator expression. Moreover, epithelial barrier function was preserved under IL‐6 stimulation, with attenuation of TEER loss, decreased paracellular permeability, and recovery of tight junction (TJ) protein levels. Several phytochemical constituents tentatively identified in AVWE by UPLC‐QTOF‐MS/MS showed favorable predicted interactions with NF‐κB. Collectively, these findings across oxidative, inflammatory, and barrier‐related endpoints support further evaluation of AVWE in experimental models relevant to IBD.