likviriton and Colitis

Inflammatory bowel disease (IBD) is a significant global health concern that can lead to depression in affected patients. Liquiritin apioside (LA) possesses anti-oxidative and anti-inflammatory properties. However, its anti-inflammatory mechanism in IBD has not been extensively studied.. This study elucidates the pivotal role of LA in alleviating inflammation by regulating gut metabiota-derived metabolites and evaluating its regulative effects on promoting a balance of Th17/Treg cells in colitis mice.. To evaluate the effect of LA on IBD,16S rRNA gene sequencing and UPLC-QTOF-MS analysis were used to identify the changes of intestinal bacteria and their metabolites. Cytokines levels were determined by ELISA and qPCR, while immune cell ratios were evaluated via flow cytometry.. Our findings revealed that LA treatment ameliorated general states of DSS-induced colitis mice and their accompanying depressive behaviors. Moreover, LA restricted the expression of pro-inflammatory cytokines and revised the imbalanced Treg/Th17 differentiation, while promoting SCFAs production in inflamed colon tissues. Fecal microbiota transplantation from LA-fed mice also corrected the imbalanced Treg/Th17 differentiation, indicating that LA-mediated restoration of the colonic Treg/Th17 balance mainly depends on the changes in gut metabolites.. These results provide scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols, and suggesting that LA could be used as a potential dietary supplement for the prevention and improvement of IBD.

Topics: Animals; Colitis; Cytokines; Depression; Humans; Inflammation; Inflammatory Bowel Diseases; Mice; RNA, Ribosomal, 16S; T-Lymphocytes, Regulatory

Inhibition of ferroptosis in intestinal epithelial cells ameliorates clinical symptoms and improves endoscopic presentations in inflammatory bowel disease (IBD). Licorice is used worldwide in food and medicine fields. Liquiritin, a flavonoid component in licorice, is an effective substance used as an anti-inflammatory, antioxidant food that has been shown to improve chemically induced colitis. Herein we evaluated the therapeutic effects of liquiritin on colitis and determined whether liquiritin could affect colitis by modulating ferroptosis in epithelial cells. A colitis model was induced in mice by oral administration with 2.5% DSS dissolved in drinking water. The results showed that liquiritin significantly alleviated symptoms, suppressed intestinal inflammation and restored the epithelial barrier function in the colitis mouse model. Liquiritin supplementation upregulated colonic ferritin expression, increased the storage of cellular iron, reduced the cellular iron level and further inhibited ferroptosis in epithelial cells from the colitis model. Pharmacological stimulation of ferroptosis largely blocked liquiritin-induced alleviation of colitis. Peroxiredoxin-6 (Prdx6) expression was significantly decreased in the DSS group, which was reversed by liquiritin treatment. Genetic or pharmacological silencing of Prdx6 largely reversed liquiritin-induced modulation of the ferritin/iron level and ferroptosis in epithelial cells. Molecular docking results showed that liquiritin could bind to Prdx6 through the hydrogen bond interaction with amino acid residues Thr208, Val206 and Pro203. In conclusion, liquiritin treatment largely alleviated DSS induced colitis by inhibiting ferroptosis in epithelial cells. Liquiritin negatively regulated ferroptosis in epithelial cells in colitis by activating Prdx6, increasing the expression of ferritin and subsequently reducing the cellular iron level.

Topics: Amino Acids; Animals; Anti-Inflammatory Agents; Antioxidants; Colitis; Dextran Sulfate; Disease Models, Animal; Epithelial Cells; Ferritins; Ferroptosis; Flavanones; Glucosides; Iron; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Peroxiredoxin VI