Ruiyan Li1, Yingying Chen2, Meijing Shi1, Xinxin Xu1, Yaxing Zhao1, Xiaojun Wu3, Yubin Zhang4. 1. State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing, China, 210009. 2. State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing, China, 210009; Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China, 201203. 3. Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China, 201203. 4. State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing, China, 210009. Electronic address: ybzhang@cpu.edu.cn.
Abstract
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 antiinflammatory 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 7.5g/kg/day and berberine (BBR, 100mg/kg/d) was selected as a positive group in the animal experiments. In vitro, GQ (25, 50, 100µg/ml) or BBR (20µM) co-cultured with RAW264.7 for 2h 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-κB activation in mucosa, which was accompanied with down regulation of several inflammatory cytokines in the colon, including tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-1β 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-α, IL-6, IL-1β 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-κB signaling and enhancement of antioxidant effect might be the potential mechanisms for the therapeutic effect of GQ against UC.
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 antiinflammatory 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 7.5g/kg/day and berberine (BBR, 100mg/kg/d) was selected as a positive group in the animal experiments. In vitro, GQ (25, 50, 100µg/ml) or BBR (20µM) co-cultured with RAW264.7 for 2h 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-κB activation in mucosa, which was accompanied with down regulation of several inflammatory cytokines in the colon, including tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-1β 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-α, IL-6, IL-1β 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-κB signaling and enhancement of antioxidant effect might be the potential mechanisms for the therapeutic effect of GQ against UC.
Authors: Mohsen Hanifeh; Satu Sankari; Minna M Rajamäki; Pernilla Syrjä; Susanne Kilpinen; Jan S Suchodolski; Romy M Heilmann; Phillip Guadiano; Jonathan Lidbury; Jörg M Steiner; Thomas Spillmann Journal: BMC Vet Res Date: 2018-04-04 Impact factor: 2.741