Phloretin Protects Bovine Rumen Epithelial Cells from LPS-Induced Injury

• Published in: Toxins 2022-05, Vol.14 (5), p.337
• Main Authors: Wang, Kexin, Lei, Qian, Ma, Huimin, Jiang, Maocheng, Yang, Tianyu, Ma, Qianbo, Datsomor, Osmond, Zhan, Kang, Zhao, Guoqi
• Format: Article
• Language: English
• Subjects: Acidosis; Animals; Anti-Inflammatory Agents - pharmacology; Antibacterial activity; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis; Bacteria; bovine rumen epithelial cells; Cattle; CCL20 protein; Chemokines; Chemokines - genetics; Chemokines - metabolism; Chemokines - pharmacology; Cytokines; Dairy cattle; Endotoxins; Enzymes; Epithelial Cells; Epithelium; Female; Flavonoids; Gene expression; Gram-negative bacteria; IL-1β; In vivo methods and tests; Indicators; Inflammation; Inflammation - chemically induced; Inflammation - prevention & control; Interleukin 6; Interleukin 8; lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Metabolites; Microorganisms; Milk production; Molecular modelling; Monocyte chemoattractant protein 1; NF-kappa B - metabolism; NF-κB protein; oxidation resistance; Oxidative stress; phloretin; Phloretin - metabolism; Phloretin - pharmacology; Physiology; Pretreatment; Protein expression; Proteins; Rumen; Rumen - metabolism; TLR4 protein; Toll-like receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Zonula occludens-1 protein
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins14050337

Lipopolysaccharide (LPS) is an endotoxin that induces immune and inflammatory responses in the rumen epithelium of dairy cows. It is well-known that flavonoid phloretin (PT) exhibits anti-oxidative, anti-inflammatory and antibacterial activity. The aim of this research was to explore whether PT could decrease LPS-induced damage to bovine rumen epithelial cells (BRECs) and its molecular mechanisms of potential protective efficacy. BRECs were pretreated with PT for 2 h and then stimulated with LPS for the assessment of various response indicators. The results showed that 100 µM PT had no significant effect on the viability of 10 µg/mL LPS-induced BRECs, and this dose was used in follow-up studies. The results showed that PT pre-relieved the decline in LPS-induced antioxidant indicators (T-AOC and GSH-PX). PT pretreatment resulted in decreased interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α) and chemokines (CCL2, CCL5, CCL20) expression. The underlying mechanisms explored reveal that PT may contribute to inflammatory responses by regulating Toll-like receptor 4 (TLR4), nuclear transcription factor-κB p65 (NF-κB p65), and ERK1/2 (p42/44) signaling pathways. Moreover, further studies found that LPS-induced BRECs showed decreased expression of claudin-related genes (ZO-1, Occludin); these were attenuated by pretreatment with PT. These results suggest that PT enhances the antioxidant properties of BRECs during inflammation, reduces gene expression of pro-inflammatory cytokines and chemokines, and enhances barrier function. Overall, the results suggest that PT (at least in vitro) offers some protective effect against LPS-induced ruminal epithelial inflammation. Further in vivo studies should be conducted to identify strategies for the prevention and amelioration of short acute rumen acidosis (SARA) in dairy cows using PT.