Shusong Wu1, Satoshi Yano1, Ayami Hisanaga1, Xi He2, Jianhua He2, Kozue Sakao1,3, De-Xing Hou1,2,3. 1. The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan. 2. Core Research Program 1515, Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, P. R. China. 3. Department of Food Science and Biotechnology, Faculty of Agriculture, Kagoshima University, Kagoshima, Japan.
Abstract
SCOPE: Nonalcoholic steatohepatitis (NASH) is a common disease, which is closely associated with inflammation and oxidative stress, and Lonicera caerulea L. polyphenols (LCP) are reported to possess both antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects and mechanisms of LCP on NASH in a high-fat diet plus carbon tetrachloride (CCL4 ) induced mouse model. METHODS AND RESULTS: Mice were fed with high-fat diet containing LCP (0.5-1%) or not, and then administrated with CCL4 to induce NASH. Liver sections were stained by hematoxylin-eosin stain, serum transaminases and lipids were measured by clinical analyzer, insulin was examined by ELISA, cytokines were determined by multiplex technology, and hepatic proteins were detected by Western blotting. LCP improved histopathological features of NASH with lower levels of lipid peroxidation and cytokines including granulocyte colony-stimulating factor, IL-3, IL-4, macrophage inflammatory protein-1β, IL-6, IL-5, keratinocyte-derived cytokine, tumor necrosis factor-alpha, IL-2, IL-1β, monocytes chemotactic protein-1, IL-13, IFN-γ, IL-10, IL-12(p70), IL-1α, eotaxin, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-1α, IL-17, and RANTES. Further molecular analysis revealed that LCP increased the expression of nuclear factor (erythroid-derived 2)-like 2 and manganese-dependent superoxide dismutase, but decreased forkhead box protein O1 and heme oxygenase-1 in the liver of NASH mice. CONCLUSION: Dietary supplementation of LCP ameliorates inflammation and lipid peroxidation by upregulating nuclear factor (erythroid-derived 2)-like 2 and manganese-dependent superoxide dismutase, and downregulating forkhead box protein O1 and heme oxygenase-1 in NASH.
SCOPE: Nonalcoholic steatohepatitis (NASH) is a common disease, which is closely associated with inflammation and oxidative stress, and Lonicera caerulea L. polyphenols (LCP) are reported to possess both antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects and mechanisms of LCP on NASH in a high-fat diet plus carbon tetrachloride (CCL4 ) induced mouse model. METHODS AND RESULTS:Mice were fed with high-fat diet containing LCP (0.5-1%) or not, and then administrated with CCL4 to induce NASH. Liver sections were stained by hematoxylin-eosin stain, serum transaminases and lipids were measured by clinical analyzer, insulin was examined by ELISA, cytokines were determined by multiplex technology, and hepatic proteins were detected by Western blotting. LCP improved histopathological features of NASH with lower levels of lipid peroxidation and cytokines including granulocyte colony-stimulating factor, IL-3, IL-4, macrophage inflammatory protein-1β, IL-6, IL-5, keratinocyte-derived cytokine, tumor necrosis factor-alpha, IL-2, IL-1β, monocytes chemotactic protein-1, IL-13, IFN-γ, IL-10, IL-12(p70), IL-1α, eotaxin, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-1α, IL-17, and RANTES. Further molecular analysis revealed that LCP increased the expression of nuclear factor (erythroid-derived 2)-like 2 and manganese-dependent superoxide dismutase, but decreased forkhead box protein O1 and heme oxygenase-1 in the liver of NASH mice. CONCLUSION: Dietary supplementation of LCP ameliorates inflammation and lipid peroxidation by upregulating nuclear factor (erythroid-derived 2)-like 2 and manganese-dependent superoxide dismutase, and downregulating forkhead box protein O1 and heme oxygenase-1 in NASH.