Protective Effect Of Naringenin On Acute Immunological Liver Injury

Immune homeostasis is necessary for the immune system to exert normal function.If activated deficiently,it may produce immune escape,on the contrary,it will produce autoimmune diseases even fatal organ damage. Uncontrolled activation of innate and adaptive immunity results in acute immunological liver injury.Although advance in the mechanisms of these diseases and critical components of inflammation,there is still lack of specific and effective treatments.Naringenin have a variety of pharmacological effects,such as scavenging free radicals,antioxidation,antibacterial,antitumor.In previous study,we found that naringenin could modulate immune function,here,we want to explore whether it could prevent acute inflammation.In this study,the models of acute immunological liver injury induced by ConA and LPS were used to evaluate the protective effect of naringenin,and the mechanisms of naringenin were investigated by Jo2-induced acute liver damage model and T lymphocyte function assays.The result showed that ALT and AST in naringenin group(950.6 U/L and 598.0 U/L) was smaller than those of in model group(1769.28U/L and 1474.4U/L, respectively) in ConA-induced acute immunological liver injury model,versus 32.88 U/L and 67.9 U/L in normal control group.TC and TG in model group increased significantly compared with normal group,whereas they in naringenin group were much lower than those in model group.In addition,pathological section showed that liver in model group had a serious damage,naringenin could improve liver damage.Tunel assay showed that there was serious liver apotosis in model group but not in naringenin group.In LPS-induced acute immunological liver injury model,serum IFN-γin naringenin group and untreatment group were 0.29ng/ml and 1.02ng/ml respectively,serum TNF-αin naringenin 200 mg/kg body weight group and 100 mg/kg body weight group were 0.307 ng/ml and 0.405 ng/ml respectively, decreased 47.16%and 62.21%respectively compared with untreatment group.In addition,serum cytokines such as IL - 6,TNF-α,IFN-γin naringenin group were significantly reduced compared with untreatment group.However,in Jo2-induced acute immunological liver injury model,serum ALT and AST showed no difference between naringenin group and untreatment group,this was further confirmed by survival of mice.Further study showed that naringenin could inhibit T cell proliferation induced by ConA,LPS and CD3 in vitro.The addition of IL-2 could be partially aborted naringenin-promoted T cell proliferation induced by CD3.The flow cytometry analysis showed that naringenin significantly decreased cytokines including IL-4,IL-2,IFN-γand TNF-αin T cell proliferation.In addition, naringenin also reduced IL-1,IL-2,IL-6 and IL-10 in CBA assay.In conclusion,our results indicated that naringenin as a immune modulator could protect immunological liver injury by inhibiting T cell activation and therefore reducing cytokines secretion...