Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4/NF-κB/NLRP3 signaling pathway in vivo and in vitro

Background: Inflammatory bowel diseases are characterized by the alterations of the mucosa and gastrointestinal physiology, and the core of these alterations is endothelial cells. Quercetin is a flavonoid presents in some traditional Chinese medicine, plants, and fruits. Its protective effects in several gastrointestinal tumors have been demonstrated, but its effects on bacterial enteritis and pyroptosis-related diseases have rarely been studied. 
Objective: This study aimed to evaluate the effect of quercetin on bacterial enteritis and pyroptosis. 
Design: In vitro experiments were performed using rat intestinal microvascular endothelial cells divided into seven groups: control group (no treatment), model group (10 μg/mL lipopolysaccharide (LPS)+1 mM adenosine triphosphate [ATP]), LPS group (10 μg/mL LPS), ATP group (1 mM ATP), and treatment groups (10 μg/mL LPS+1 mM ATP and 5, 10, and 20 μM quercetin). The expression of pyroptosis-associated proteins, inflammatory factors, tight junction proteins, and the percentage of late apoptotic and necrotic cells were measured. In vivo analysis was performed using specific pathogen-free Kunming mice pretreated with quercetin and the water extract of Cacumen Platycladi for 2 weeks followed by 6 mg/kg LPS on day 15. Inflammation in the blood and intestinal pathological changes were evaluated. 
Results: Quercetin used in vitro significantly reduced the expression of Toll-like receptor 4 (TLR4), NOD-like receptor 3 (NLRP3), caspase-1, gasdermin D, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor-α. It also inhibited phosphorylation of nuclear factor-kappa B (NF-κB) p65 and increased cell migration and the expression of zonula occludens 1 and claudins, while reduced the number of late apoptotic cells. The in vivo results showed that Cacumen Platycladi and quercetin significantly reduced inflammation, protected the structure of the colon and cecum, and prevent fecal occult blood induced by LPS. 
Conclusions: These findings suggested the ability of quercetin to reduce inflammation induced by LPS and pyroptosis through TLR4/NF-κB/NLRP3 pathway.