Hydroxypropyl Methylcellulose as a Functional Dietary Fiber Preserves Intestinal Barrier Integrity via NF-κB Modulation Under Inflammatory Conditions

Abstract

Intestinal epithelial barrier integrity is crucial for maintaining gut homeostasis and preventing luminal inflammation. Disruption of tight junctions (TJs) by pro-inflammatory cytokines such as tumor necrosis factor-α and interferon-γ contributes to barrier dysfunction, a hallmark of disorders like inflammatory bowel disease. In this study, we investigated the protective effects of hydroxypropyl methylcellulose (HPMC), a widely used excipient and dietary fiber, against cytokine-induced epithelial barrier dysfunction in Caco-2 cell monolayers. HPMC treatment preserved transepithelial electrical resistance, reduced paracellular leakage of FITC-dextran, and significantly suppressed the secretion of inflammatory mediators, including interleukin (IL)-8, IL-1β, IL-6, and monocyte chemoattractant protein (MCP)-1. Furthermore, HPMC restored the expression and localization of TJ proteins zonula occludens-1 and occludin and attenuated NF-κB activation by inhibiting IκBα phosphorylation and subsequent nuclear translocation. These findings indicate that HPMC counteracts cytokine-driven epithelial barrier disruption through coordinated anti-inflammatory and barrier-stabilizing actions. Collectively, our results demonstrate that noncytotoxic HPMC (12.5–100 μg/mL) has potential as a safe pharmaceutical excipient and functional dietary fiber capable of supporting intestinal health under inflammatory conditions.