Protective Effect Of Maltol On Experimental Liver Injury And Its Antitumor Activity

Maltol?Maltol,3-hydroxy-2-methyl-4-pyrone,C₆H₆O₃?,a kind of natural aroma compounds,is widely derived from present in soybeans,coffee,chicory,bread and caramel food.It is a product of maltose and amino acids generated by the Maillard reaction.At the same time it is also the unique component of red ginseng.Red ginseng,a ginseng belongs to the traditional Chinese medicine,genus apiales,Araliaceae ginseng?Panax ginseng C.A.Meyer?roots and rhizomes,can be cooked products through infiltration,cleaning,sorting,steaming,drying,It has many beneficial effect,like nourishing vitality Fumai solid off,tonifying qi and blood effect.The Maillard reaction in processing time?Maillard reaction?,shows the appearance of the smell and color of fresh ginseng and thus produce a change,meanwhile produce pharmacological activity--maltol,it is also a special component of red ginseng.The antioxidant activity of Maltol is known,and to its strong scavenging the radicalability strong.Not only can effectively protect against oxidative stress induced damage of neurons,but can prevent kidney damage caused by diabetes.And it can also improve liver injury of mice induced via alcohol by inhibiting oxidative stress and inflammatory reaction.In this study,we established experimental liver injury and H₂₂ liver tumor model of mice through the pharmacological activity study about Maltol exists in red ginseng.Furthermore,we explore effect of Maltol on liver tissue anti-tumor activity in vivo.This paper firstly established the acute liver injury model of mice induced by carbon tetrachloride.For in vivo examination,male ICR mice were randomly divided into four groups:Normal group,CCl₄ group,Maltol group and CCl₄+Maltol group.Maltol intragastric treatment?100 mg/kg BW?were administered continuously for 15days.The CCl₄ and CCl₄+Maltol groups were given an intraper injection of 0.25%eintraperitoneal injection?i.p.?of CCl₄ result in increased serum aspartate aminotransferase?AST?,alanine aminotransferase?ALT?,a nuclear transcription factor?NF-?B?,tumor necrosis factor-??TNF-??and interleukin-1??IL-1??levels.Histopathological examination showed the model group had serious necrosis of liver cells and hepatic diseases.Immunohistochemical staining revealed significantly enhanced expression of NF-?B and TNF-?.However,maltol administrayion can reverse these changes.Addionally Hoechst 33258 stining results showed that the model group of nuclear proliferation in uniform fluorescence is visualized in CCl₄model group.However,there is no observed condensation and fragmentation in maltol prettrnment group.To detect the expression of CYP2E1 in liver toxicity induced by CCl₄ staining by immunofluorescence,staining CCl₄ cause cell apoptosis and expression of CYP2E1 increased significantly,where as maltol pretreatment group can significantly improve these pathological changes.These results showed that Maltol pretreatment can pretreatment can prevent CCl₄-induced.Liver injury will be transformed into sever in a serious extent.liver cancer We observed anti-tumor effect of maltol in vivo through the establishment of H₂₂ liver cancer transplant tumor model.Male ICR mice were randomly divided into Normal group,Model group,CTX group and maltol group?25 mg/kg and 50mg/kg?.The results showed that maltol could not only inhibit the growth of H₂₂ tumor,but prolong the survival time of H₂₂ tumor-bearing mice.In addition,the levels of cytokines in serum of H₂₂ tumor-bearing mice were reduced,such as interferon gamma?IFN-??,tumor necrosis factor-??TNF-??,interleukin-2?IL-2?and Interleukin-6?IL-6?,these indexs are enhanced by treatment with maltol.The decrease in vascular endothelial growth factor?VEGF?levels was improved after treatment with maltol.Hoechst33258 staining and TUNEL staining showed that maltol could induce apoptosis of H₂₂tumor cells.Immunohistochemical analysis and Western blot analysis showed that the anti-tumor effect of maltol was expressed in a dose-dependent manner.In general,our finding showed that found in this experiment,maltol on H₂₂ tumor-bearing mice have an inhibitory effect,with a strong anti-tumor effect in vivo.In summary,the experimental results in this study show that maltol can effectively inhibit the inflammatory response,reduce serum ALT,AST activity,inhibition of apoptosis,thereby it reduce CCl₄-induced liver injury.In this study,we explore the antitumor effect and possible molecular mechanism of maltol on H₂₂tumor-bearing mice for the first time,our result demonstrated that Maltol can significantly inhibit the growth of H₂₂ tumor in ascites transplantation model and have obvious anti-tumor effect on H₂₂ tumor bearing mice partly through the improvement of immune function,induction of apoptosis and inhibition of vascular regeneration.It means that maltol can be used as a new drug for the treatment of liver disease,and its development prospects are very optimistic due to the pharmacological activity,which has in-depth study of Maltol components great significance.