Polyphenols from Lonicera caerulea L. berry attenuate experimental nonalcoholic steatohepatitis by inhibiting proinflammatory cytokines productions and lipid peroxidation

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.

Keywords: Cytokines; HO-1; Lipid peroxidation; Lonicera caerulea L; Nonalcoholic steatohepatitis; Nrf2; Polyphenols.