The Impact of Quercetin and Its Methylated Derivatives 3-o-Methylquercetin and Rhamnazin in Lipopolysaccharide-Induced Inflammation in Porcine Intestinal Cells

Abstract

Oxidative stress in the small intestine can lead to inflammation and barrier malfunction. The present study describes the effect of quercetin (Q), 3-o-methylquercetin (QM), and rhamnazin (R) on cell viability, paracellular permeability, production of intracellular reactive oxygen species (ROS), extracellular hydrogen peroxide (H2O2), and interleukin-6 (IL-6) after challenging jejunal cells (IPEC-J2) with different types (Salmonella enterica ser. Typhimurium, Escherichia coli O111:B4, and E. coli O127:B8) of lipopolysaccharides (LPS) applied in 10 µg/mL concentration. The intracellular ROS level increased after all LPS treatments, which could be decreased by all tested flavonoid compounds in 50 µM concentration. Extracellular H2O2 production significantly increased after Q and R treatment (50 µM). S. Typhimurium LPS could significantly increase IL-6 production of enterocytes, which could be alleviated by Q, QM, and R (50 µM) as well. Using fluorescein isothiocyanate dextran (FD4) tracer dye, we could demonstrate that S. Typhimurium LPS significantly increased the permeability of the cell layer. The simultaneous treatments of S. Typhimurium LPS and the flavonoid compounds showed no alteration in FD4 penetration compared to untreated cells. These results highlight that Q, QM, and R are promising substances that can be used to protect intestinal epithelial cells from the deteriorating effects of oxidative stress.

Luteolin and Chrysin Could Prevent E. coli Lipopolysaccharide-Ochratoxin A Combination-Caused Inflammation and Oxidative Stress in In Vitro Porcine Intestinal Model

“…The Amplex red method, in contrast to DCF, is only suitable for the detection of H 2 O 2 , whereas the latter is a non-selective ROS detecting method. In IPEC-J2 cells, LPS of various origins could not increase H 2 O 2 levels [ 38 ] using Amplex red method which is in good agreement with our present findings. Other mycotoxins such as DON and T2 toxin and their combination could increase EC H 2 O 2 in IPEC-J2 cells, which returned to control levels in the presence of rosmarinic acid [ 39 ].…”

Quercetin Improves Barrier Properties in Porcine Small Intestine but Not in Peyer’s Patches

“…Furthermore, in a combined incubation of quercetin and TNFα, quercetin was able to mitigate the barrierweakening effect of TNFα. Also, in IPEC J2 cells, different incubation challenges were performed and showed a barrier-protective effect of quercetin against barrier perturbation by, e.g., lipopolysaccharide (LPS) [59] or deoxynivalenol (DON) [60,61]. In contrast to our IPEC J2 results, Pomothy [60] and Li et al [61] observed an increased TEER due to quercetin incubation without any challenge.…”

Plant-Derived Polyphenols as Nrf2 Activators to Counteract Oxidative Stress and Intestinal Toxicity Induced by Deoxynivalenol in Swine: An Emerging Research Direction

“…Quercetin (C 15 H 10 O 7 ), a flavonoid, is abundantly present in vegetables and fruits as a secondary antioxidant metabolite [ 38 ]. Quercetin has a strong antioxidant capacity, which gives it a perfect preventive and therapeutic effect on diseases caused by oxidative stress [ 55 ]. The antioxidant property of quercetin was previously proven in the porcine intestine in vitro and in vivo experiments.…”

“…Using a specific inhibitor of Nrf2 (all-trans-retinoic acid), the authors further demonstrated that the protective effect of quercetin on enterocytes was mediated via activating the Nrf2 signaling pathway and redox homeostasis [ 60 ]. Karancsi et al (2022) reported the protective impact of quercetin and its methylated derivatives on inflammation in IPEC-J2 cells, acting against the lipopolysaccharide challenge [ 55 ]. A dosage of 50 μM quercetin or its methylated derivatives all decreased intracellular ROS levels, extracellular H 2 O 2 levels, and IL-6 levels of IPEC-J2 cells challenged with lipopolysaccharide [ 55 ].…”

“…Karancsi et al (2022) reported the protective impact of quercetin and its methylated derivatives on inflammation in IPEC-J2 cells, acting against the lipopolysaccharide challenge [ 55 ]. A dosage of 50 μM quercetin or its methylated derivatives all decreased intracellular ROS levels, extracellular H 2 O 2 levels, and IL-6 levels of IPEC-J2 cells challenged with lipopolysaccharide [ 55 ]. The aforementioned results highlight that quercetin could be used as a promising substance to protect the intestine against oxidative stress.…”