Bioactive Peptides Derived From Chinese Acid-Curd Cheeses: A Comprehensive Review of Formation, Identification,...

Chinese acid-curd cheeses (CACCs) are known for their long history and distinctive acidification process. Although they are recognized as important sources of bioactive peptides (BPs), a comprehensive synthesis of current knowledge on the formation, bioactivity, and structure-activity relationships of CACC-derived bioactive peptides (CACCBPs) remains limited. To address this gap, this review summarizes and critically evaluates recent advances in the generation, identification, functional properties, and potential applications of CACCBPs. CACCBPs are predominantly generated through acid hydrolysis and microbial proteolysis of caseins, with β-casein serving as the primary precursor. The integration of peptidomics, molecular docking, network pharmacology, and complementary bioinformatics tools has significantly advanced the discovery and characterization of these peptides. CACCBPs exhibit a wide range of health-promoting properties, including antioxidant, hypoglycemic, antihypertensive, and immunomodulatory activities. Mechanistic studies revealed that CACCBPs exert their effects by modulating key signaling pathways (e.g., Keap1-Nrf2 and Nrf2/NF-κB/MAPK/PHD-2) and by interacting with potential receptors (e.g., Keap1, ACE, and α-glucosidase). This review also provides a systematic discussion of structure-activity relationships, emphasizing the roles of molecular weight, amino acid composition, and hydrophobicity in determining peptide function. Despite their promise, challenges remain in large-scale production, in vivo efficacy verification, and peptide stability improvement. Future research should integrate advanced technologies and interdisciplinary approaches, conduct comprehensive clinical evaluations of safety and efficacy, investigate absorption and metabolic pathways in detail, and enhance the stability and bioavailability of peptides to support their practical application in functional foods and health products.