Yu_2025_Food.Res.Int_221_117338

This study aimed to develop a functional oyster peptide-chitosan oligosaccharide (COS)zinc complex (OCZn) with enhanced bioactivity and explore its structural characteristics, interaction mechanisms, and protective effects against zinc deficiency. OCZn showed dispersion and enlarged particle size and covered zinc signals. Protein P86788-derived peptides offered the highest Transglutaminase (TGase)-induced glycosylation peptides (over 8.6 %) where glutamine provided more glycosylated sites than lysine. Furthermore, four representative amino acid sequences (3 to 4 kDa) were selected from P86788 interacted with COS at DP levels (2-4) determined by molecular docking. The covalent bonds at TGase-induced sites and hydrogen bonds were responsible in formation of peptides-COS complex while it linked to zinc through oxygen atoms in the carbonyl, hydroxyl, and sugar ring groups in peptides and COS. In zinc deficiency-induced mice model, high dose of OCZn restored neuronal integrity in the hippocampus. In addition, the level of acetylcholine (ACh) in the hippocampus of mice was significantly elevated, accompanied by a decrease in the activity of acetylcholinesterase (AChE). Furthermore, Western blot analysis demonstrated an enhancement in the expression of both synaptic structural protein (PSD95) and alpha-synaptic nucleoprotein (alpha-Syn). OCZn demonstrated antioxidant effects against cellular oxidative stress, mitochondrial membrane potential disorders, and apoptosis in TM3 cells. This study elucidated the precise molecular mechanism underlying TGase-induced glycosylated peptidezinc complexes, confirming their dual neuroprotective and antioxidant efficacy. Furthermore, it provided both a theoretical foundation and a practical strategy for the development of targeted zinc supplements.