Quercetin Alleviates Lipopolysaccharide-Induced Cell Damage and Inflammation via Regulation of the TLR4/NF-κB Pathway in Bovine Intestinal Epithelial Cells

Abstract

Acute diarrhoea and intestinal inflammation represent one of the most prevalent clinical disorders of milk production, resulting in enormous annual financial damage for the dairy sector. In the context of an unsatisfactory therapeutic effect of antibiotics, the natural products of plants have been the focus of research. Quercetin is an important flavonoid found in a variety of plants, including fruits and vegetables, and has strong anti-inflammatory effects, so it has received extensive attention as a potential anti-inflammatory antioxidant. However, the underlying basis of quercetin on inflammatory reactions and oxidative tension generated by lipopolysaccharide (LPS) in bovine intestinal epithelial cells (BIECs) is currently unexplained. This research aimed to determine the influence of quercetin on LPS-induced inflammatory reactions, oxidative tension, and the barrier role of BIECs. Our findings demonstrated that BIEC viability was significantly improved in LPS-treated BIEC with 80 μg/mL quercetin compared with the control group. Indicators of oxidative overload and genes involved in barrier role revealed that 80 μg/mL quercetin efficiently rescued BIECs from oxidative and barrier impairment triggered by 5 μg/mL LPS. In addition, the mRNA expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as chemokines CXCL2, CXCL5, CCL5, and CXCL8, was diminished in LPS-treated BIECs with 80 μg/mL quercetin compared with LPS alone. Furthermore, the mRNA expression of toll-like receptor 4 (TLR4), CD14, myeloid differential protein-2 (MD2), and myeloid differentiation primary response protein (MyD88) genes associated with the TLR4 signal mechanism was markedly reduced by the addition of quercetin to LPS-modulated BIECs, indicating that quercetin can suppress the TLR4 signal mechanism. We performed Western blotting on the NF-κB signalling mechanism and compared it with immunofluorescence to further corroborate this conclusion. The LPS treatment enhanced the proportions of p-IκBα/GAPDH and p-p65/GAPDH. Compared with the LPS-treated group, quercetin administration decreased the proportions of p-IκBα/GAPDH and p-p65/GAPDH. In addition, immunofluorescence demonstrated that quercetin greatly reduced the LPS-induced nuclear translocation of NF-κB p65 in BIECs. The benefits of quercetin on inflammatory reactions in LPS-induced BIECs may be a result of its capacity to inhibit the TLR4-mediated NF-κB signalling mechanism. These findings suggest that quercetin can be used as an anti-inflammatory reagent to treat intestinal inflammation induced by LPS release.

Revealing the potential bioactive components and mechanism of Qianhua Gout Capsules in the treatment of gouty arthritis through network pharmacology, molecular docking and pharmacodynamic study strategies

“…Another study demonstrated that Nobiletin upregulates PPARG, PPARA, and CXCL8 levels, while inhibiting MMP9 expression and suppressing the release of inflammatory factors TNF-α and IL-6, also achieving anti-inflammatory effects [ 59 ]. Quercetin, a common flavonoid constituent, exhibits potent anti-inflammatory activity by acting as a PPARG agonist to reduce MSU-induced inflammation, block NF-kB activation, and down-regulate the production and expression of IL-1β, IL-6, and MMP9 [ [60] , [61] , [62] ]. Wogonin effectively inhibits migration, invasion, and production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, MMP-3, and MMP-9) in RA fibroblast-like synoviocytes through the PI3K/AKT/NF-κB pathway.…”

Quercetin Protects Blood–Brain Barrier Integrity via the PI3K/Akt/Erk Signaling Pathway in a Mouse Model of Meningitis Induced by Glaesserella parasuis

“…Quercetin has also been reported to mitigate Pseudomonas aeruginosa -induced acute lung inflammation by decreasing the production of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α [ 37 ]. Furthermore, quercetin treatment has been shown to notably lower the mRNA expression levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in lipopolysaccharide (LPS)-induced bovine intestinal epithelial cells (BIECs) [ 38 ]. We examined the changes in mRNA expression of inflammatory factors ( Il-1β , Il-6 , Il-8 , Il-10 , Il-18 , and Tnf-α ) in G. parasuis -infected mice, both in vivo and in vitro.…”

Discovering the Protective Effects of Quercetin on Aflatoxin B1-Induced Toxicity in Bovine Foetal Hepatocyte-Derived Cells (BFH12)

“…A potential application of QUE in treating bovine viral diarrhoea virus infection has been explored in Madin–Darby bovine kidney cells (MDBK) [ 48 ]. Likewise, QUE’s anti-inflammatory potential has been demonstrated in bovine intestinal epithelial cells (BIECs) [ 49 ] and mammary epithelial cells (BMECs) [ 50 ]. The above-mentioned studies provided important molecular results to disentangle QUE’s mechanism of action in cattle, thus increasing the fundamental knowledge that is necessary to introduce QUE-supplemented feed in farming practice.…”