Ultrasonic modification on the physicochemical properties, structure characterizations, and intestinal barrier-protective activities of raspberry polysaccharides

Natural polysaccharides possess diverse biological functions, yet their macromolecular architecture frequently restricts molecular accessibility and limits their application as health-promoting ingredients. Here, we employed an ultrasound-driven strategy to remodel the molecular structure of raspberry polysaccharide (RAP) and investigated how controlled depolymerization governs its intestinal barrier-protective properties. Native RAP was subjected to ultrasonic irradiation for 2 and 5 h, generating two structurally tailored derivatives, RAP-2 and RAP-5. Ultrasonic processing progressively decreased the molecular size of RAP from 10.47 kDa to 8.79 and 5.94 kDa, respectively, without disrupting its monosaccharide profile or fundamental chemical framework. Structural analyses revealed that ultrasound-induced cavitation promoted polysaccharide chain scission, leading to a transition from compact aggregates toward fragmented and porous architectures. Importantly, molecular remodeling translated into enhanced biological functions. In an LPS-challenged Caco-2/THP-1 macrophage co-culture model, RAP-5 exhibited superior capacity to preserve epithelial barrier integrity, restoring TEER values to 93.28% while markedly attenuating inflammatory mediator release, including IL-6 (65.49 pg/mL), TNF-α (271.63 pg/mL), and IL-1β (94.91 pg/mL). Moreover, RAP-5 effectively recovered the expression of barrier-associated genes, increasing ZO-1 and Occludin transcripts to 0.89- and 0.82-fold of the control levels, respectively. Collectively, these findings demonstrate that controlled ultrasonic remodeling represents an efficient approach for optimizing the structure-function relationship of RAP, providing new opportunities for developing polysaccharide-based functional foods targeting intestinal homeostasis.