2. Academic Validation
  3. Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ

Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ

  • J Agric Food Chem. 2023 Dec 28. doi: 10.1021/acs.jafc.3c05714.
Weijia Li 1 2,  Haoming Li 1 2,  Jiaqi Song 1 2,  Yihang Xing 1 2,  Li Fang 1 2,  Xiyan Wang 1 2,  Dan Wu 1 2,  Weihong Min 3
Affiliations

Affiliations

  • 1 College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, P.R. China.
  • 2 National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, P.R. China.
  • 3 College of Food and Health, Zhejiang A&F University, Hangzhou 311300, P.R. China.
PMID: 38155399 DOI: 10.1021/acs.jafc.3c05714
Abstract

We investigated the absorption mechanism of the shrimp peptide QMDDQ in small intestines, explored its physiological function in inhibiting neuronal hyperactivity, and verified its entry into the brain in vivo to display functional activity. The everted rat sac model and a Caco-2 paracellular absorption monolayer model were used, indicating that QMDDQ has a good absorption capacity with an apparent permeability coefficient (Papp) > 1 × 10-6 cm/s and the absorption of QMDDQ was concentration-dependent. When the concentration of QMDDQ was 1 mM and the transport time was 180 min, the highest absorption concentration of QMDDQ was 41.17 ± 3.48 μM (P < 0.05). The Myosin light-chain kinase (MLCK)-specific inhibitor ML-7 and activator MPA, Western blotting, and immunofluorescence results showed that QMDDQ absorption takes place by mediating the MLCK-p-MLCK-MLC signaling pathway, reversibly opening the zonula occludens-1 (ZO-1), occludin in tight junctions (TJs), upregulating claudin-2 expression, and reaching targets through blood to inhibit neuronal overactivity. Results of fluorescence imaging in vivo verified that QMDDQ could enter the brain 4 h after oral administration. The results provide a theoretical foundation for the mechanism of paracellular absorption of active Peptides and a starting point for the development of functional foods for Alzheimer's disease intervention.

Keywords

MLCK; neuronal hyperactivity; paracellular absorption; shrimp peptide.

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