original data.rar

Inhibition
of ferroptosis in intestinal epithelial cells ameliorates
clinical symptom and improves endoscopic presentations in inflammatory
bowel disease (IBD). Liquiritin is a main effective ingredient of Glycyrrhiza Radix, which has been
applied as a therapeutic strategy in China for thousands of years, and could
significantly ameliorate chemically induced colitis. However, whether
liquiritin could affect IBD still remains unclear. Herein we evaluated the
effects of liquiritin on colitis and whether liquiritin could affect IBD by
modulating ferroptosis in epithelial cells. Colitis model was induced in mice
by oral treatment with 2.5% DSS dissolved in drinking water. Results showed
that liquiritin significantly alleviated symptom, suppressed intestinal inflammation
and restored epithelial barrier function in colitis mice model. Liquiritin
supplementation upregulated colonic ferritin expression, increasing the storage
of cellular iron, reducing cellular iron level and further inhibited
ferroptosis in epithelial cells from colitis model. Pharmacological stimulation
of ferroptosis largely blocked liquiritin-induced alleviation of colitis.
Peroxiredoxin-6 (Prdx6) expression was significantly decreased in DSS group,
which was reversed by liquiritin treatment. Genetic or pharmacological
silencing of Prdx6 largely reversed liquiritin-induced modulation of
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-induced activation of Prdx6 led to
reduction of cellular iron content, and further inhibition of epithelial
ferroptosis.