Quercetin Alleviates Lipopolysaccharide-Induced Inflammatory Response in Bovine Mammary Epithelial Cells by Suppressing TLR4/NF-κB Signaling Pathway

Abstract

Bovine mastitis is one of the most common clinical diseases in dairy cows, causing huge economic losses to the dairy industry. Quercetin is an important flavonoid existing in many food resources, which has attracted widespread attention as a potential anti-inflammatory and antioxidant. However, the molecular mechanism of quercetin on inflammatory responses and oxidative stress in bovine mammary epithelial cells (BMECs) induced by lipopolysaccharide (LPS) remains unknown. The objective of this study was to investigate the effects of quercetin on inflammation responses, oxidative stress, and barrier function of BMEC induced by LPS. Our results showed that BMEC viability was not affected by treatment with 50 and 100 μg/ml of quercetin and 1 μg/ml of LPS compared with control group. The results of oxidative stress indicators and related genes of barrier function indicated that 100 μg/ml of quercetin effectively protected the BMECs from damage of oxidative and barrier induced by 1 μg/ml of LPS. Moreover, the messenger RNA (mRNA) expressions of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and chemokines CXCL2, CXCL5, CCL5, and CXCL8 were markedly decreased in the LPS-treated bovine retinal endothelial cells (BRECs) with 100 μg/ml of quercetin relatively to LPS alone. More importantly, the mRNA expressions of toll-like receptor 4 (TLR4), CD14, myeloid differential protein-2 (MD2), and myeloid differentiation primary response protein (MyD88) genes involved in TLR4 signal pathway were significantly attenuated by the addition of quercetin in LPS-treated BMEC, suggesting that quercetin can inhibit the TLR4 signal pathway. In addition, immunocytofluorescence showed that quercetin significantly inhibited the nuclear translocation of NF-κB p65 in BMEC induced by LPS. Therefore, the protective effects of quercetin on inflammatory responses in LPS-induced BMEC may be due to its ability to suppress the TLR4-mediated NF-κB signaling pathway. These findings suggest that quercetin can be used as an anti-inflammatory reagent to treat mastitis induced by exogenous or endogenous LPS release.

Quercetin Alleviates Lipopolysaccharide-Induced Cell Oxidative Stress and Inflammatory Responses via Regulation of the TLR4-NF-κB Signaling Pathway in Bovine Rumen Epithelial Cells

“…Excessive oxidative stress stimulates inflammatory cells, which leads to inflammation. The currently available research points to a connection between oxidative stress and inflammation [ 35 , 36 ]. Inflammatory cells contribute to oxidative stress via reactive oxygen species (ROS), but ROS might additionally promote the generation of inflammatory cytokines [ 37 ].…”

Evaluation of the mechanism of Gong Ying San activity on dairy cows mastitis by network pharmacology and metabolomics analysis

“…The Chinese traditional medicine formulation, Gong Ying San has been used as a mastitis treatment for many years [ 34 , 35 ]. The Dandelion , Lonicera japonica flos , and Forsythia fructus in this recipe are cooling and thus detoxify the body, disperse wind, and reduce heat.…”

Diverse and Synergistic Actions of Phytochemicals in a Plant-Based Multivitamin/Mineral Supplement against Oxidative Stress and Inflammation in Healthy Individuals: A Systems Biology Approach Based on a Randomized Clinical Trial

“…Known for its antioxidant and anti-inflammatory capabilities, quercetin functions as a scavenger of ROS and reactive nitrogen species, enhancing the body's antioxidant defense [20]. It also diminishes the cytokine production induced by the lipopolysaccharide and gene expression of pro-inflammatory markers such as tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8), through the inhibition of TLR-mediated NF-κB signaling pathways [21][22][23]. Ellagic acid contributes to lipid peroxidation inhibition, free radical neutralization, and the reduction in inflammatory cytokines and chemokines, such as TNF-α and IL-6, while suppressing NF-κB expression [24,25].…”