Biological Activity of Plant-Derived Peptides, Hydrolysates and Digests in the Caco-2 Intestinal Epithelial Model: A Systematic Critical Review
Abstract
Plant-derived bioactive peptides are widely investigated for their effects on intestinal epithelial function using Caco-2 cells, with reported antioxidant, anti-inflammatory, antihypertensive and antidiabetic activities. However, this literature remains heterogeneous and has rarely addressed whether the tested material corresponds to the actual bioactive species. This PRISMA-compliant systematic review searched PubMed and Scopus for studies on plant-derived peptides, hydrolysates or digests in Caco-2 cells, identifying 34 eligible studies. The material tested in each study was classified a priori as a purified or synthetic single peptide, an ultrafiltration or chromatographic fraction, a whole hydrolysate or gastrointestinal digest, or an intact parent protein used as a comparator, because these forms do not support equivalent structure-activity inference. Risk of bias was assessed using the QUIN tool, adopted in the absence of an instrument validated for nutritional cell-culture research. For each study, metabolic characterisation of the tested peptide and the physiological relevance of the concentrations used were evaluated. Directionally consistent bioactivity, including antioxidant, anti-inflammatory, antihypertensive and antidiabetic effects, was observed across most functional domains, although effect magnitude and stress dependence varied considerably. Mass-based concentrations did not uniformly exceed a conservative exploratory luminal benchmark (0.1-1 mg/mL), but…
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Evidence Hub reads this as a systematic review, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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