Plant Polyphenol-Polysaccharide Complexes for Inflammatory Bowel Disease: Molecular Interactions, Nano-Delivery...

Plant polyphenol-polysaccharide complexes (PPCs) combine polyphenol bioactivity with the protective, mucoadhesive, and microbiota-accessible properties of polysaccharides. However, the literature often groups chemically distinct polyphenols together, extrapolates structure-function relationships across nonequivalent carriers, and interprets concurrent microbiota or short-chain fatty acid changes as causal mechanisms.

This review critically evaluated how molecular interactions and measurable structural attributes of PPCs influence gastrointestinal stability, colon-oriented release, biological effects relevant to inflammatory bowel disease (IBD), and translational readiness.

Targeted searches of PubMed, Web of Science Core Collection, Scopus, Embase, and the Cochrane Library were completed through July 20, 2026. Peer-reviewed original studies and relevant reviews published in English were considered.

Evidence was classified as direct PPC evidence, PPC-relevant formulation evidence, or non-PPC mechanistic and engineering evidence. Information on carrier chemistry, payload, structural attributes, release behavior, biological outcomes, and translational considerations was extracted.

Quantitative findings were compared only when carrier chemistry, payload, test conditions, and outcomes were sufficiently aligned; heterogeneous data were not pooled. Non-covalent assembly and covalent conjugation can alter molecular organization, physicochemical stability, and release, but no universal relationship between degree of substitution and release is supported. Epigallocatechin-3-gallate, quercetin, and anthocyanins require compound-specific carrier selection. PPC and PPC-relevant interventions are associated with changes in NF-κB-related signaling, epithelial-barrier markers, microbiota composition, and individual short-chain fatty acids, whereas receptor- or microbiota-mediated causality remains largely unverified. Responsive platforms also differ in stability, release control, scale-up burden, and clinical readiness.

PPC-based nano-delivery is a promising preclinical approach, but translation requires matched studies linking structure, properties, and release, mediator-level mechanistic validation, standardized characterization, reproducible manufacturing, formulation-specific safety assessment, and comparison with established IBD therapies.