Sanguinarine Enhances the Integrity of the Blood–Milk Barrier and Inhibits Oxidative Stress in Lipopolysaccharide-Stimulated Mastitis

Abstract

Mastitis is a common clinical disease which threatens the welfare and health of dairy cows and causes huge economic losses. Sanguinarine (SG) is a plant-derived alkaloid which has many biological functions, including antibacterial and antioxidant properties. The present study attempted to evaluate the effect of SG on lipopolysaccharide (LPS)-induced oxidative stress reactions and explore its potential mechanisms. The expression profile of SG was analyzed by network pharmacology, and it was found that differentially expressed genes were mainly involved in the Wnt signaling pathway and oxidative stress through GO and KEGG enrichment. In in vitro experiments, the dosage of SG was non-toxic to mouse mammary epithelial cells (mMECs) (p > 0.05). SG not only inhibited the increase in ROS induced by LPS, but also enhanced the activity of antioxidant enzymes (p < 0.05). Moreover, the results of the in vivo experiments showed that SG alleviated LPS-induced inflammatory damage of mouse mammary glands and enhanced the integrity of the blood–milk barrier (p < 0.05). Further studies suggested that SG promoted Nrf2 expression and suppressed the activation of the Wnt signaling pathway (p < 0.05). Conclusively, this study clarified the protective effect of SG on mastitis and provided evidence for new potential mechanisms. SG exerted its antioxidant function through activating Nrf2 and inhibiting the Wnt/β-catenin pathway, repairing the blood–milk barrier.

Dietary supplementation with Macleaya cordata extract alleviates intestinal injury in broiler chickens challenged with lipopolysaccharide by regulating gut microbiota and plasma metabolites

“…Similarly, dietary supplementation of 200 mg/kg MCE observably alleviated oxidative stress induced by enterotoxigenic Escherichia coli in mice, as illustrated by lower levels of MDA and increased activities of CAT and GSH-Px ( 18 ). It has been reported that sanguinarine not only decreased the ROS level induced by LPS, but also increased the activity of antioxidant enzymes by activating the Nrf2 signaling pathway in mouse mammary epithelial cells ( 34 ). Moreover, sanguinarine can inhibit the activities of nicotinamide adenine dinucleotide phosphate oxidase 2, thereby inhibiting the conversion of NADPH to ROS and improving the antioxidant capacity ( 35 ).…”

Ginseng polysaccharides promote gut microbiota mediated deoxycholic acid to alleviate LPS-induced mastitis by regulating TGR5-cAMP-PKA-NF-κB/NLRP3 pathway

“…Mastitis not only causes a quantity of economic losses in the global dairy industry every year, but also brings enormous pain to lactating women [2,3]. The causes of mastitis are diverse, among which bacterial invasion is considered one of the main reasons, and Gram-negative bacteria is considered to the main pathogen [4].…”