Red-Osier Dogwood Extracts Prevent Inflammatory Responses in Caco-2 Cells and a Caco-2 BBe1/EA.hy926 Cell Co-Culture Model

Abstract

Red-osier dogwood extracts (RDE) contain high levels of phenolic compounds which have been recognized as natural antioxidants. In this study, the potential of RDE to prevent cardiovascular diseases (CVDs) was evaluated using Caco-2 cells and a co-culture model of Caco-2 BBe1/EA.hy926 cells in Transwell® plates. The results showed that RDE supplementation significantly prevented interleukin-8 (IL-8) production and suppressed the gene expression of IL-8, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and cyclooxygenase 2 (COX-2) in the TNF-α inflamed Caco-2 cells. Meanwhile, the polyphenols (quercetin-3-glucoside, quercetin-glucuronide, rutin, quercetin-3-O-malonylglucoside, and kaempferol-glucoside) in the RDE were validated to be absorbed by Caco-2 BBe1 cells and transported to the basal chamber where EA.hy926 cells were located during 12 h incubation. The transported polyphenols were able to prevent IL-8 production and suppress the gene expression of proinflammatory mediators (TNF-α, ICAM-1, VCAM-1, and COX-2) in the TNF-α or oxidized low-density lipoprotein (ox-LDL) treated EA.hy926 cells. These novel findings demonstrated that phenolic compounds in RDE can be transported to the cardiovascular system by intestinal absorption and mitigate the inflammatory responses of vascular endothelial cells, indicating that RDE could be a natural resource of polyphenols to prevent inflammation cytokine or oxidized lipid-induced CVDs.

Mitochondria-Targeted Antioxidants: A Step towards Disease Treatment

“…In the cases of overloaded oxidative stress, a timely supplement of antioxidants to maintain the normal function of the cardiovascular system is crucial for the prevention and treatment of cardiovascular diseases. Some conventional antioxidants such as CoQ10 [ 120 ], polyphenols [ 121 ], vitamin C [ 122 ], and vitamin E [ 123 ] have been shown to prevent and treat cardiovascular disease in models, with expanded ongoing clinical trials ( NCT03133793 , NCT01925937 , NCT02779634 , NCT02847585 , NCT02934555 , and NCT02218476 ). However, the majority of these clinical studies are in unknown status which might be attributed to the poor biopharmaceutical properties and the pharmacokinetics of the nontargeted antioxidants.…”

4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model

“…Another one has shown that IPEC-J2 cells with 0.2 μg/mL DON exposure exhibited lower cell viability and mRNA levels of tight junction proteins, such as ZO-1, occludin, and claudin-1 ( Liao et al., 2017 ). Transwell plates have been widely used for establishing the in vitro models of epithelial barriers to mimic the actual in vivo conditions ( He et al., 2019 ; Jiang et al., 2019 ). In the present study, we firstly screened an optimal concentration of DON to induce intestinal barrier damage of the IPEC-J2 monolayer in the transwell plates.…”

“…The procedure for TEER measurement was described in our previous study ( Jiang et al., 2019 ). Briefly, after equilibrating the cells with PBS for 10 min at room temperature, an electrical resistance monitor (ESR-2, Millipore, USA) was used for TEER measurement.…”

“…Weaning stress ( Moeser et al., 2007 ), mycotoxin-contaminated feed ingestion ( Pierron et al., 2016 ), and Escherichia coli infection ( Ewaschuk et al., 2011 ) cause defective intestinal barrier functions in pigs. This subsequently increases intestinal permeability and endotoxins penetrating the intestine-blood barrier ( Jiang et al., 2019 ), which triggers long-lasting inflammatory responses and reduces growth performance ( Broom and Kogut, 2018 ). Feed additives supplements, such as polysaccharides, oligosaccharide, chitosan, and probiotics have been revealed to benefit intestinal barrier function and promote the growth performance of piglets ( Hu et al., 2018 ; Wan et al., 2018 ; Wang et al., 2019a ; Yi et al., 2018 ).…”

Dietary Application of Tannins as a Potential Mitigation Strategy for Current Challenges in Poultry Production: A Review

“…However, if there is an imbalance between oxidants and antioxidants in chickens, excessively produced ROS can impair gut health and induce inflammation, which results in decreased growth performance of chickens [ 115 ]. Antioxidants including plant extracts [ 116 , 117 ], L-carnitine [ 118 ], vitamin C [ 119 , 120 ], vitamin E [ 121 ], and selenium [ 122 ] have been studied to alleviate heat stress and oxidative stress.…”