Efficacy and Mechanism of Quercetin in the Treatment of Experimental Colitis Using Network Pharmacology Analysis

Abstract

Quercetin, a flavonoid that is present in vegetables and fruits, has been found to have anti-inflammatory effects. However, the mechanism by which it inhibits colitis is uncertain. This study aimed to explore the effect and pharmacological mechanism of quercetin on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). Mice were given a 4% (w/v) DSS solution to drink for 7 days, followed by regular water for the following 5 days. Pharmacological mechanisms were predicted by network pharmacology. High-throughput 16S rDNA sequencing was performed to detect changes in the intestinal microbiota composition. Enzyme-linked immunosorbent assay and western blotting were performed to examine the anti-inflammatory role of quercetin in the colon. Quercetin attenuated DSS-induced body weight loss, colon length shortening, and pathological damage to the colon. Quercetin administration modulated the composition of the intestinal microbiota in DSS-induced mice and inhibited the growth of harmful bacteria. Network pharmacology revealed that quercetin target genes were enriched in inflammatory and neoplastic processes. Quercetin dramatically inhibited the expression of phosphorylated protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K). Quercetin has a role in the treatment of UC, with pharmacological mechanisms that involve regulation of the intestinal microbiota, re-establishment of healthy microbiomes that favor mucosal healing, and the inhibition of PI3K/AKT signaling.

Beneficial Effects of Hordenine on a Model of Ulcerative Colitis

“…Each well was given the medication for 24 h before the addition of 10 μL CCK-8 reagent and an additional hour of incubation. The aforementioned test was carried out three times [ 33 ]. It was found that 500, 250, 125, 62.5, 31.25, and 15.625 μM of hordenine had no significant effect on the survival rate of MCEC cells for 24 h. Therefore, 500 μM was chosen as the hordenine administration condition.…”

“…All mice were then randomly divided into six groups ( n = 10/group): untreated control, DSS model, DSS+5-ASA 40 mg/kg, and DSS+hordenine 50 mg/kg, DSS+hordenine 25 mg/kg, DSS+hordenine 12.5 mg/kg ( Figure 1 B). Except for the control group, mice were given 4% ( w / v ) DSS solution for 7 days before being given regular water for the next 5 days [ 33 ]. From day 1 to day 12, mice in the treatment groups were administered 5-ASA or hordenine daily by gavage, while mice in control and DSS model groups were administered normal saline.…”