Study On Pharmacodynamic Process Evaluation And Mechanism Of Polygonum Perfoliatum L. Against Chemical Liver Injury

The Polygonum perfoliatum L. is one pecies of Polygonaceae,and which is used in folk medicine.It is mainly used for the treatment of gynecological inflammation and the curative effect is significant.The latest research found that it has the effect of anti-chemical liver although it specific process and molecular mechanism are not clear.This paper is under the guidance of traditional Chinese medicial science includ five elements theory and viscera theory,three important organs of kidney,liver and heart were selected as the research object to establish the chemical liver injury model induced by carbon tetrachloride.Combined with modern pharmacological technology,the pharmacodynamic process evaluation of it anti-chemical liver injury was carried out to fuuly understand the specific process of its.Based on the traditional target and liposome technology,the mechanism of anti-chemical liver injury was studied,and the molecular mechanism of anti-chemical liver injury was clarified,so as to provide scientific and technological support for the scientific understanding of P.perfoliatum.The method used KM male mice were injected intraperitoneally with4%carbon tetrachloride olive oil solution every 3 days to establish the model of liver injury in the Study on the pharmacodynamic process evaluation of P.perfoliatum until the end of the experiment.After the two weeks when the establishment of the model,the positive group and the administration group were given intragastric administration of biphenyl double ester and alcohol extract suspension of P.perfoliatum.Every 3days according to the intragastric volume of 10 ml·kg^-1,respectively.The mice in the blank group were injected intraperitoneally,intragastrically and intragastrically with the same volume of normal saline instead of the model group.After 1 week,2 weeks,3 weeks and 4 weeks of administration,the body weight,organ index,serum AST,ALT,LDH activity and BUN content were taken as indexes,and the pathological morphology of liver,heart and kidney was observed,so as to evaluate the pharmacodynamic process of anti-chemical liver injury and reveal the effect of liver on its upstream and downstream organs--heart and kidney.The results show that the extract of P.perfoliatum can improve the injury of hepatocytes to a certain extent,reduce the release of liver enzymes,significantly reduce the activity of liver enzymes in mice with CCl₄ liver injury,reduce the pathological damage of liver tissue,and show obvious hepatoprotective effect.With the increase of the administration time of P.perfoliatum,the injury degree of CCl₄ to the liver of mice slightly aggravated,but did not increase significantly,which may be related to the injection interval of the model and the self-healing ability of mice.Compared with P.perfoliatum administration group at different administration time nodes,it was found that with the increase of administration time,the protective ability of P.perfoliatum return to chemical liver injury in mice was enhanced,and its efficacy was positively correlated with the administration time.The pharmacodynamic process showed that there was a regulating trend after 1 week of administration,but there was no significant improvement,and the effect of significant improvement on liver injury was 2 weeks after administration,and the hepatoprotective effect reached a better level after3 weeks of administration.The efficacy of P.perfoliatum return was not significantly improved after 4 weeks of administration,but tended to be stable and remained at a good level.The heart and kidney,as the upstream and downstream organs of the liver,were also affected by liver injury,which was related to the severity and time of liver injury.Significant damage was found in the heart and kidney of mice in the model group only after 2 weeks of administration.The liver injury in the positive group and the administration group may be maintained at a certain level due to the protection and treatment of liver injury,but did not continue to aggravate.Furthermore,the heart and kidney of the mice in the positive group and the administration group were not seriously damaged.Study on the mechanism of anti-chemical liver injury of P.perfoliatum based on traditional target the activity of SOD,GPS-Px and the content of MDA in the liver of mice at different time points were determined by ELISA kit.The results showed that the protective mechanism of alcohol extract of P.perfoliatum on chemical liver injury in mice was closely related to increasing the activity of antioxidant system and reducing the production of lipid peroxidation products.After 2 weeks of administration,the content of MDA in the liver of mice in the treatment group decreased significantly,while the activities of SOD and GPS-Px increased significantly.The hepatoprotective effect reached the best after 3 weeks of administration,and tended to be stable after 4 weeks of administration.Study on the mechanism of anti-chemical liver injury based on liposomics UPLC-Orbitrap/MS was used to detect the lipid content in liver,blood,heart and kidney of mice at different time points of the above experimental animals.The results showed that chemical liver injury was mainly related to the disorder of glycerophospholipid metabolism,followed by sphingolipid metabolism and glycerolipid metabolism.Through the study on the regulation of lipid molecules between the blank group and the model group when the P.perfoliatum was given for 4weeks,it was found that most of the lipids in the administration group showed a tendency to change to the normal level.The mechanism of chemical liver injury is mainly related to glycerol phospholipid metabolism.The effective and stable lipid data for 4 weeks were selected to study the mechanism of anti-chemical liver injury.It was found that there were significant changes in the expression levels of 89 kinds of lipids in the liver of mice in the blank group and the model group.After administration with P.perfoliatum,the contents of 8 lipids,PC（18:0/20:3）,Cer（d18:2/16:0）,PE（18:2/22:6）,PE（19:0/22:6）,CL（18:2/18:2/18:2/18:2）,PI（19:0/20:4）,PIP（54:6）and SM（d41:1）,were significantly higher than those in the model group（P<0.05）.The results showed that the extract of P.perfoliatum could effectively improve chemical liver injury and significantly improve the abnormality of liver lipid metabolism in mice with chemical liver injury,especially on glycerol phospholipid metabolism.Therefore,it is speculated that the regulation of the activity of enzymes related to glycerol phospholipid metabolism pathway may be its mechanism,and its exact mechanism needs to be further studied.Through the pathway enrichment analysis of significant differences in lipids in liver,serum,heart and kidney of mice for 4 weeks,three common metabolic pathways were found.Among them,only glycerophosphate metabolism was found when impact>0.1 of metabolic pathway.Therefore,the upstream and downstream organs of the liver（heart and kidney）may be due to abnormal glycerol phospholipid metabolism in the liver,and signal molecules are transmitted to the heart and kidney through the blood,which to some extent affect the glycerophospholipid metabolism of the heart and kidney and disorder its metabolism.So this may be the reason why the heart and kidney are also affected to a certain extent after liver injury,and the heart and kidney are also protected after drug intervention to improve liver injury.