Cow Placenta Peptides Ameliorate D-Galactose-Induced Intestinal Barrier Damage by Regulating TLR/NF-κB Pathway

This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group (T), and a vitamin C treatment g...

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Main Authors: Yuquan Zhao, Zhi Zeng, Weijian Zheng, Zeru Zhang, Hanwen Zhang, Yuxin Luo, Kunshan Zhao, Yuyan Ding, Wei Lu, Fuxing Hao, Yixin Huang, Liuhong Shen
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Veterinary Sciences
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Online Access:https://www.mdpi.com/2306-7381/12/3/229
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Summary:This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group (T), and a vitamin C treatment group (P). Groups T and P received oral administration of CPP (2000 mg/kg/day) and vitamin C (100 mg/kg/day), respectively, while groups M, T, and P were subjected to intraperitoneal injections of D-galactose (D-gal) (300 mg/kg/day). Group N received an equivalent volume of normal saline via intraperitoneal injection. Treatments were administered once daily for 8 weeks. The results demonstrated that CPP significantly alleviated D-galactose-induced intestinal structural damage, increasing the villus height-to-crypt depth ratio and reducing serum diamine oxidase (DAO) and lipopolysaccharide (LPS) levels. CPP notably alleviated intestinal oxidative stress and inflammation, restored tight junction expression, and enhanced intestinal barrier integrity. Transcriptome sequencing identified 1396 DEGs associated with CPP’s effects, highlighting <i>TLR4</i>, <i>IL-1β</i>, and <i>Mmp9</i> as core regulatory genes through protein–protein interaction network analysis. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses implicated the TLR4/NF-κB signaling pathway, which was further validated. Western blotting confirmed that CPP significantly down-regulated TLR4, IKKβ, and p-NF-κB p65 protein expression in the intestines of aging mice. In conclusion, CPP effectively alleviates D-gal-induced intestinal barrier damage in aging mice by enhancing antioxidant defense and inhibiting the TLR4/NF-κB signaling pathway, thereby diminishing inflammation and protecting intestinal barrier integrity.
ISSN:2306-7381