# Anti-Inflammatory Effects of Flavonoids in an LPS-Induced In Vitro Model of Canine Chronic Enteropathy

## TL;DR

This study shows that plant compounds like quercetin, luteolin, and grape seed extract can reduce inflammation and oxidative stress in dog intestinal tissue, suggesting potential benefits for dogs with chronic gut issues.

## Contribution

The study is the first to demonstrate the anti-inflammatory and antioxidant effects of flavonoids in an in vitro model of canine chronic enteropathy.

## Key findings

- Quercetin, luteolin, and grape seed extract reduced inflammatory signals and oxidative molecules in LPS-stimulated canine intestinal tissue.
- Grape seed extract decreased reactive nitrogen species even without inflammation.
- Quercetin and luteolin specifically lowered key immune signals like TNF-α and IL-6.

## Abstract

Dogs with long-lasting intestinal problems often have an overactive immune response and a weakened gut barrier, which allows bacterial components to trigger inflammation and tissue damage. This study examined whether three natural plant compounds—quercetin, luteolin, and grape seed extract—can reduce these harmful reactions. Small sections of dog intestine were maintained in the laboratory and exposed to bacterial molecules that typically induce inflammation. When the plant compounds were added, all three helped reduce inflammatory signals and lowered the production of harmful oxidative molecules. Grape seed extract also decreased another type of reactive compound, even without an inflammatory trigger. Quercetin and luteolin were particularly effective in lowering key immune signals linked to chronic gut disease. These findings suggest that these natural substances may help support intestinal health in dogs by calming inflammation and reducing oxidative stress. Further studies in living animals are needed to confirm their potential benefits.

Background: Chronic inflammatory enteropathies (CIEs) in dogs are multifactorial disorders characterized by mucosal immune dysregulation, compromised epithelial barrier function, and increased exposure to microbial components such as lipopolysaccharide (LPS). The resulting oxidative stress and inflammation contribute to local and systemic pathology. Objective: This study aimed to evaluate the immunomodulatory and antioxidant effects of three naturally occurring flavonoids—quercetin, luteolin, and grape seed extract oligomeric proanthocyanidins (GSOPs)—in LPS-stimulated canine duodenal explants. Methods: Duodenal tissue samples were cultured in vitro and challenged with LPS derived from Escherichia coli and Salmonella enterica. Explants were co-incubated with flavonoid compounds, and endpoints included evaluation of histological architecture, inflammatory cytokine production, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Results: All three flavonoids attenuated LPS-induced mucosal inflammation and ROS production to varying degrees. In addition, GSOPs significantly reduced RNS levels under both basal and LPS-stimulated conditions. Quercetin and luteolin demonstrated pronounced downregulation of TNF-α, while both compounds also reduced IL-6 concentrations under non-stimulated conditions. These effects support the hypothesis that flavonoids can mitigate both inflammatory and oxidative responses under conditions relevant to CIE. Conclusion: Quercetin, luteolin, and GSOPs show promising in vitro efficacy in modulating key mechanisms implicated in canine CIE. Their multimodal actions highlight their potential as adjunctive nutraceuticals for the management of CIE in dogs. However, further in vivo validation is warranted.