Protective Effects Of Caffeic Acid Phenethyl Ester Derivates Against Experimental Hepatotoxicity In Rats

Background and Purpose: Caffeic acid phenethyl ester (CAPE) is amajor active component of propolis, which belongs to polyphenoliccompounds, and is a strong antioxidant and has the free radical scavengingfunction, boasting unique physiological and pharmacological effects ofanti-tumor, antioxidant, anti-inflammatory, immune regulation andischemia-reperfusion protection. A good many reports and literature havebeen proved that the CAPE pharmacological activity is related to thepresence of o-dihydroxy. Through the modification of CAPE orthodihydroxy, a derivative of caffeic acid phenethyl ester, i.e. p-Nitro caffeicacid phenethylester is obtained. Since it has the reactive groups that CAPEhas, It is deduced that the caffeic acid phenethyl ester derivatives-p-Nitrocaffeic acid phenethylester should also have some CAPE-relatedpharmacological activity.The present research applies CCl4-induced liver injury model, givingcaffeic acid phenethyl ester derivatives and observing the protective effectof the p-Nitro caffeic acid phenethylester upon the liver injury, andbringing out a preliminary exploration of its mechanism of action. Thepurpose of this experiment is to find a new therapeutic substance for curingthe CCl4-induced chemical liver injury of mice.Method: For the present research, fifty Kunming rats are randomly divided into five groups, each into10for one group. Normal control group:intraperitoneal injection of saline0.1ml/10g for each; model control group:intraperitoneal injection of saline0.1ml/10g for each; p-Nitro caffeic acidphenethylester, of high, middle and low doses of the experimental groupswere injected intraperitoneally nitro of benzene ethyl by2.0mg/kg,1.0mg/kg,0.5mg/kg for each respectively. After15consecutive days, thenormal group were injected with olive oil solution (0.1ml/10g), theremaining groups had intraperitoneal injection of0.15%CCl4olive oil thesolution (0.1ml/10g). After another24hours, orbital blood, the serum wasseparated by centrifugation and determination of AST, ALT levels. Thenexecute the rats, take the liver weight, calculate the liver index; Take theright liver lobe of10%liver homogenate,determination of the activity ofMDA,SOD,GSH-Px and CAT;Take the left hepatic lobe with10%paraformaldenyde fixed, for histopathological examination.Results:(1)In comparison to model groups, each of the CAPE-NO2ones can reduce the serum AST and ALT levels of CCl4-induced acute liverinjury of mice, and was measured at their reliability(P<0.05);(2)each of theCAPE-NO2ones can be reduced due to CCl4-induced acute liver injuryliver tissue of MDA content(P<0.05);(3)And it can increase the activity ofSOD,CAT,GSH-Px in liver tissue and the degree of this depends upon thequantity of injection(P<0.05);(4)In comparison to model groups, each ofthe CAPE-NO2ones can reduce the mice’s liver index;(5)In comparison tomodel groups, each of the CAPE-NO2ones can reduce the liver cells todifferent degrees of degeneration and necrosis, among which big scale ofdosages of CAPE-NO2have relatively slight injury, mainly waterdegeneration with occasional necrosis;(6)High or low dosage groups haveobvious decrease of mice apoptosis of liver cells in contrast to modelgroups, the differences have statistical significance (P＜0.01). Conclusions：p-Nitro caffeic acid phenethylester has protective effectsupon chemical liver injury of mice, its mechanism may be assisciated withthe liver cell apoptosis, the free radical scavenging, the reduction of thebody’s antioxidant and the inhibition of apoptosis. However, its mechanismis apt and open to further exploration.