Effect And Mechanism Of Curcuma Aromatica On Acute Liver Injury Mice Produced By CCl₄

A lot of factors can lead to the liver damage, and these factors include the external injury, chemistry hurt and the virus hepatitis etc.. Among them the liver hurt caused by virus hepatitis is most for familiar. It is the important measure to prevent liver cell from damaging for preventing hepatitis and curing chronic liverish Although there are some experiences traditional Chinese medicine, a small quantity of the Chinese patent medicine which demonstrate higher curative effects and less side effects.The CCl4 is one of the most commonly used hepatotoxins in experimental study of liver diseases . Lipid peroxidative degradation of biomembranes is one of the principal causes of hepatotoxicity of CCl4 . Lipid peroxidation is caused by the carbon trichloromethyl radical, CCl3 . CCl4 is biotransformed by cytochrome P450 to the trichloromethyl free radical that induces membrane lipid peroxidation and disturbs Ca2+ homeostasis to produce hepatocellular injury.Among the various mechanisms involved in the hepatotoxic effect of carbon tetrachloride (CCl4), one is oxidative damage through free radical generation. The antioxidant property is claimed to be one of the mechanisms of hepatoprotective effect.Curcuma aromatica is a kind of plant of the genus Curcuma. WarmCurcuma, curcuma and Curcuma kwangsiensis S.Lee et C.F.Liang or The dried tuberous root of Epicurzerenone have a long medicinal history. Modern research turns out that Curcuma aromatica Salisb have immunity of repress, cholesterol-lowering, the anti-oxidize, anti- fungi, anti- tumor, protecting liver and repressing axis etc. variouspharmacology activities. It can be used for angina pectoris, hepatitis, old age stupid, malignant tumor etc. disease. However, the effect and mechanism of Curcuma aromatica aginst liver injuries has not been clarified. We have studied the effect and mechanism of Curcuma aromatica against liver injuries, in order to elucidate new pharmacological action and new medicinal value, and furnish the theoretical basis for developing and exploiting new drug from Curcuma aromatica against liver injuries . For observing the protection function and the function mechanism of Curcuma aromatica Salisb fighting against the acute liver hurts of the small rat caused by four chlorination carbons, this experiment did the study as follows:Methods:The experimental, male and female with equal quantity,60 animals, cleaned by ICR, were randomly divided into 6 groups by weight :control group ,model group ,drug positive group(Ganlixin), Curcumae group high, middle, low groups (10g/kg,5g/kg,2.5g/kg).The first group was not treated with CCl4 treatment and served as the control. The model mice of acute hepatic injury were set up by giving intraperitoneal injection of 0.2% CCl4 (0.2ml/10mg). Ganlixin group(25mg·kg-1) and there three therapeutic groups of Curcumae which were intragastric at the doses of 2.5g·kg-1,5g·kg-1 10g·kg-1once everyday.7 days later all mice were put to death. blood was taken from the back eyepit, separated the serum, measured the level of AST and ALT in the serum, a soma piece of liver was taken 0.5cm far from the edge of lobes of liver , put into the 10%formal fixed for pathologic test another 0.5g hepatic tissue was washed by 4℃normal saline, made to be 10%liver homogenate with PBS and measured the MDA and SOD. To research the effects of Parviflora compound on the expression of nuclear factor-KB (NF-KB), IL-2,IL-4 and IL-18.Result: The level of AST,ALT in serum and MDA in liver increased , SOD in liver decreased , and had obvious difference compared with the control group(p<0.01),which suggested the establishment of the model successful, The level of AST,ALT in serum and MDA in liver decreased in Curcumae high,middle,low group , and had obvious difference compared with the model group(p<0.05, p<0.01). SOD obviously increased, and had obvious difference compared to the model group(p<0.05, p<0.01).the liver index of Curcumae group decreased compared with model group. The result of histopathology: The control group: the structure of the liver lobule was clear; there was no hepatocyte degeneration necrosis. The model group: the structure of liver lobule was damaged remarkably, there were many necrosis places the hepatocyte became broadly fatty degeneration, and many inflammation cells in them, and the formation of fibrosis could be dose group and drug control: the degree of hepatocyte degeneration, necrosis had been relieved remarkably. The result of immunohistochemistry: To examine the expression of caspase-3,NF- kB,IL-2,IL-4 and IL-18 proteins in model- CCl4, activated cells were fixed and examined by immunocytochemistry for the presence . The cells of model group showed positive staining for these proteins compared to control group. As expected, IL-2,IL-4 and IL-18 were readily detectable, while caspase-3,NF- kB expression was absent in the majority of cells, verifying the activated HSC phenotype. curcumae group's tubertreatment produced no positive signal. These data confirm at the protein level the gene expression data demonstrating that caspase-3,NF- kB,IL-2,IL-4 and IL-18 are expressed by activated CCl4.Conclusions:Curcumae could decreased the activities of ALT and AST in serum, the content of MDA in liver tissue of CCl4-induced acute liver injury mice pretreated with curcumae markedly decreased, while the liver index was decreased, The mechanism maybe involved in reducing the production of the free radicals, inhibiting the reaction of lipid peroxidation, protecting the membrane of hepatic cell. These findings were supported by the detection of caspase-3,NF- kB,IL-2,IL-4 and IL-18 expression in diseased liver tissue.It turns out from the above words that the Curcuma aromatica has the protective effects to CCI4-induced acute liver injury. Its function mechanism is related to anti- oxidize, clearance of free radicals, stability of the cell membrane, repression of expression of inflammatory cells, anti- Apoptosis .