Protective Effect And Mechanisms Of Panaxadiol Saponins Ginsenoside And Rg₅ On Acetaminophen-induced Liver Injury

Acetaminophen（APAP）is widely used analgesic and febrifuge.In a lot of clinical cases,the liver could be injured or collapsible due to overdose of drugs.It is a great threat to the health of human beings.Ginseng is known as "king of herbs" and it belongs to Araliaceae.There are many benefits of ginseng,such as the functions of organs,soothing the nerves,fixing the mind,eliminating the scarceness,and increasing the intelligence level.To improve the efficiency of the pharmacological activity of drugs,We frequently steaming and heating to change its chemical composition by steaming and neating process.Especially during the steaming process,the Rg₅ can be produced.It is known for Ginsenoisde is anticancer,anti-inflammatory effects for the human bodies.Ginsenoside Rg₅ can inhibit the secretion of inflammatory cytokines,Due to anti-inflammatory role in inhibiting cell apoptosis,and promote cell regeneration.Based on the pharmacological characteristics of ginseng,we made a in depth study of hepatoprotective effect on ginsenoside Rg3 and ginsenoside Rg₅.The first experiment was to study the effect of the Panaxadiol Saponins（PDS）on APAP and how it will protect the mice with liver-dysfunctions.32 male ICR mice were randomly divided into several groups,the control group,APAP group（Normal）,and PDS（150 mg/kg and 300 mg/kg）+ APAP group.Continuously gave drugs under7 d in PDS.One hour later,inject of the 250 mg/kg APAP into the bodies of mice group.The purpose of that is to damage the livers of the mice in that group.After 24 hours,evaluate the change of the function of the livers by observing the changes of serum ALT and AST levels.Next,check the changes in the level of hepatic GSH and change in oxidant stress,in liver tissues of mice to evaluate the level of detection.Then,evaluate the liver tissue inflammation level of TNF-α and IL-1β.In addition,check the H&E,Hoechst 33258,immunohistochemical staining（Bax）and immunofluorescence staining（CYP2E1）and observe the pathological changes in renal tissues,apoptosis and the inhibition of oxidant stress.The results showed that,compared with the model group,the serum levels of ALT,AST,TNF-α and IL-1βsignificantly decreased in the mice pretreated with PDS,and the levels of GSH in liver tissue increased,and the degree of liver injury was improved.Therefore,we suggest that PDS has protective effects on APAP induced liver injury in mice,and itsmechanism may be related to the improvement of oxidant stress,inflammation and apoptosis.The second experiment was to study the protective effect of ginsenoside Rg₅ on liver injury induced by acetaminophen（Acetaminophen,APAP）in mice and its possible mechanism.In experiment done on animals,the researcher put the essence amount of ginseng ginsenoside Rg₅ that was administrated by 10mg/kg and 20mg/kg for 7 days.After the last administration of 1h,the liver injury was induced by intragastrically injection of mg/kg at 250 APAP,and serum indexes were detected after 24 h.The results show that,compared with the model group,ginsenoside Rg₅ can effectively reduce the serum of ALT and AST levels,improve liver GSH level,and reduce the malondialdehyde（MDA）level.In addition,ginsenoside Rg₅ can significantly inhibit the increase of inflammatory factors such as TNF-and IL-1 in liver tissue,and decrease the expression of Bax,Caspase3,CYP2E1,4-HNE,3-NT,iNOS,thus increasing the expression of Bcl-2.In general,the possible mechanism of inhibition of APAP induced liver injury by ginsenoside Rg₅ is through inhibition of lipid peroxidation,nitration and anti-apoptosis,anti-inflammatory,etc.PDS will happen hydrolysis,generating a rare ginsenoside Rg₅ in high temperature environment,In order to increase the conversion rate of Rg₅,and optimizing the process,we select the glycol group of ginsenoside Rb₁ for transformation,and perform the orthogonal experiment analysis,to select the optimal process conditions.In summary,our findings showed that PDS protect APAP-induced hepatic intoxication by the reduction levels of ALT and AST,the suppression of hepatocyte apoptosis,the decrease of lipid peroxidation and the expression of inflammatory cytokines.The ginsenoside Rg₅ obtained by panaxadiol ginsenosides hydrolysis in acidic environment on liver injury in mice induced by APAP has some improvement mechanism mainly is to repair cell membrane of mitochondrion,decrease the permeability of cell membrane,and increased blood transaminase activity.It inhibited the oxidation stress and increased the content of GSH,thereby protecting the liver.