Downregulation of iNOS and elevation of cAMP mediate the anti-inflammatory effect of glabridin in rats with ulcerative colitis

Alternative medicine is widely accepted by public and becoming an attractive approach for treatment of various diseases. Glabridin (Gla), a major flavonoid present in licorice root, was reported to have antioxidant and anti-inflammatory properties. The study aimed to investigate the possible protective role of Gla against dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in rats and to clarify the molecular mechanisms underlying Gla function. Forty male Wistar rats were divided into control, colitis group (rats received 5% DSS in drinking water for 7 days), Gla group (50 mg/kg, orally, once daily), and sulfasalazine (SLZ) group (500 mg/kg, orally, once daily). Each of Gla and SLZ was administered 1 week ahead of DSS and parallel with its administration. Gla ameliorated the inflammatory alterations induced by DSS. Gla group showed a reduction in colon concentration of tumor necrosis factor-alpha (TNF-alpha) and a decreased colon myeloperoxidase activity (MPO). Gla treatment downregulated inducible nitric oxide synthase (iNOS) gene expression in rat colon with a decreased content of nitric oxide (NO). Gla also increased cyclic AMP (cAMP) concentration in rat colon compared to colitis group. Such findings were comparable to or even better than those obtained by SLZ treatment. The histological features of UC such as ulceration and inflammatory cell infiltrations were improved in rat group treated by Gla. Gla proved a potent anti-inflammatory role in UC through different mechanisms and, being a natural product, it could be safely used as a protective measure in inflammatory bowel diseases.