Cinnamaldehyde alleviates LPS-induced endoplasmic reticulum stress-mediated barrier damage in IPEC-J2 by regulating...

Early weaning-induced intestinal barrier dysfunction is a major contributor to post-weaning diarrhea, growth retardation, and increased mortality in piglets, resulting in substantial economic losses and heavy reliance on antibiotic use in swine production. Cinnamaldehyde (Cin) is a plant essential oil that has been shown to promote intestinal health and may offer a potential alternative to antibiotics.

To investigate the probable mechanism underlying Cin's mitigating action on LPS-induced impairment of the integrity of the pig's small intestine epithelial barrier.

IPEC-J2 cells were used as a model with four different treatment groups, and a 10 μM dose of Cin was selected to establish the model for alleviating intestinal barrier damage. After 24 h, barrier integrity, cell function, IP₃R, ER stress markers, and intracellular Ca²⁺ were measured.

Cin alleviated LPS-induced cell cycle arrest, apoptosis, and proliferation inhibition. It restored barrier function, as evidenced by increased TEER, reduced FITC-Dextran 4 permeability, and upregulated expression of TJs. Mechanistically, Cin suppressed LPS-induced ER stress and ER expansion, downregulated IP₃R expression, and reduced cytosolic Ca²⁺ overload. Correlation network analysis identified IP₃R as a key link between ER stress and barrier dysfunction.

In summary, this study is the first to demonstrate that Cin exerts therapeutic effects on the injured IPEC-J2 barrier by regulating calcium homeostasis via IP₃R. This study proposes new treatment strategies for restoring intestinal homeostasis disrupted by weaning stress in piglets.