Gegen Qinlian decoction alleviates experimental colitis via suppressing TLR4/NF-κB signaling and enhancing antioxidant effect

Background: Gegen Qinlian decoction (GQ), a Chinese medicinal herb decoction, has been widely used as efficient medicine for the treatment of acute colitis in clinics, but underlying molecular mechanisms have not been fully clarified. Hypothesis/purpose: Inflammation and oxidative stress have been reported to constitute a crucial part in the pathogenesis of ulcerative colitis (UC). Hence, this study was designed to investigate the anti-inflammatory activity and antioxidative effect of GQ. Study design: Mice induced by 5% dextran sulfate sodium (DSS) and macrophage RAW264.7 cells stimulated by lipopolysaccharide (LPS) were used in this study. Methods: Ethanol extracts of GQ were orally administered for 1 week on the dosage of 0.3, 1.5, or 7.5 g/kg/day and berberine (BBR, 100 mg/kg/d) was selected as a positive group in the animal experiments. In vitro, GQ (25, 50, 100 mu g/ml) or BBR (20 mu M) co-cultured with RAW264.7 for 2 h prior to LPS stimulation. Results: The results showed that GQ oral administration alleviated the severity of colitis notably. It reduced toll-like receptor 4 (TLR4) expression and NF-kappa B activation in mucosa, which was accompanied with down regulation of several inflammatory cytokines in the colon, including tumor necrosis factor (TNF-alpha), interleukin (IL)-6, IL-1 beta and IL-4. Furthermore, GQ oral administration attenuated the oxidative stress in the colon of UC mice, evidenced by the decrease of myeloperoxidase (MPO) activity and malondialdehyde (MDA) level, and the elevation of glutathione (GSH) content. In parallel with the vivo experiment results, cell research indicated GQ dramatically reduced the production of TNF-alpha, IL-6, IL-1 beta and nitric oxide (NO), as well as that of reactive oxygen species (ROS) upon stimulation of LPS. Conclusion: Together, our present study indicates that inhibition of TLR4/NF-kappa B signaling and enhancement of antioxidant effect might be the potential mechanisms for the therapeutic effect of GQ against UC. (C) 2016 Elsevier GmbH. All rights reserved.