Magnesium isoglycyrrhetate inhibits the over-release of inflammatory mediators in LPS-stimulated macrophages through up-regulating heme oxygenation-1
Zhang Lei
Jiang Lei
Zhang Li-kun
Gong Rui
Pan Shang-ha
Zhao Ming-yan
Abstract：Objective To investigate whether magnesium isoglycyrrhetate (MgIG) can inhibit high mobility group box-1 protein (HMGB1) and nitric oxide (NO) release by up-regulating heme oxygenase-1 (HO-1) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages.Methods RAW264.7 macrophages stimulated with LPS were used as inflammatory cell models.①The cells were treated with LPS and different concentrations of MgIG for 24 hours firstly:the control group,LPS group and LPS + MgIG groups (0.01 mg/mL,0.10 mg/mL,0.50 mg/mL and 1.00 mg/mL).Secondly,the cells were randomly divided into the control group,LPS group,LPS + MgIG (1.00 mg/mL) group and LPS + MgIG (1.00 mg/mL) + ZnPPIX (10 μmol/L) group.The level of HMGB1 in the supernatant was measured by ELISA.The concentration of NO in the supematant was measured by Griess method.The expression of HO-1 and iNOS protein was detected by Western blotting.Results ①Compared with the control group,LPS significantly increased the levels of HMGB1 and NO in the supernatant (P ＜0.05),and increased the expression of HO-1 protein (P ＜0.05).Compared with the LPS group,the levels of HMGB1 and NO in the supernatant were both decreased with the increased dose of MgIG (P ＜ 0.05),while the expression of HO-1 was significantly increased with the increased dose of MgIG (P ＜0.05).②Compared with Control,LPS also significantly increased the concentration of HMGB1 and NO in supernatant (P ＜ 0.05),and notably increased HO-1 and inducible nitric oxide synthase (iNOS) protein expression (P＜0.05).Compared with the LPS group,the levels of HMGB1 and NO in the supernatant and iNOS protein expression in the cell were all markedly decreased by MgIG (1.00 mg/mL) (P ＜ 0.05),while the HO-1 protein expression in the cell was significantly augmented (P ＜ 0.05).However,no differences were detected between the LPS group and LPS + MgIG (1.00 mg/mL) + ZnPPIX(10 μ mol/L) (P ＞ 0.05).Conclusion MgIG inhibits the over-release of HMGB1 and NO and the protein expression of iNOS via up-regulation of HO-1 in LPS-stimulated macrophages.
Keywords：Magnesium isoglycyrrhetate (MgIG)Heme oxygenase-1 (HO-1)High Mobility Group Box 1 (HMGB1)Nitric oxide (NO)Sepsis
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 983-987 )