Mechanism For Total Triterpenoids Of Prunella Vulgaris L. On Protective Of Actue Liver Injury And Hepatic Fibrosis Of Rats

The liver is an metabolism and biotransformation organ in our body. It susceptibleto be invasion by pathogens and stimulating factors stimulatied, for rich blood supply,which lead to liver damage and inflammation. Clinical cause of acute liver injurymainly due to inappropriate drug use, excessive drinking, eating toxic food, and viralinfections. The mechanism of liver damage isquite complex, can be divided intochemical and immunity. Produce damage to the chemical mechanism of metabolicintermediates by CYP2E1and the binding reaction, such as mitochondrial dysfunction,change the integrity of the plasma membrance, intracellular ion concentration changes,as well as free radical; immune mechanisms by cytokines, carbonmonoxide,the complement and immune hypersensitivity injury, pathologic apoptosis is one ofthem.The liver long time is at the damage condition, often lead to liver fibrosis（hepaticfibrosis）. Hepatic fibrosis is regarded as a pathologically repair reaction followedvarious kinds of chronic liver diseases. It is characterized by an excessive deposition ofextracellular matrix proteins（ECM） of which type I collagen predominates. Hepaticfibrosis is a common stage of most chronic liver diseases regardless of the etiology, andits progression may lead to hepatic cirrhosis or hepatocelluar carcinoma（HCC）.Although hepatic fibrosis thought to be a reversible pathological state, there is no established effective therapy for hepatic fibrosis yet. Many anti-fibrosis drugs have beendeveloped in recent years. However, no effective anti-fibrotic therapies are availableuntil now. Accordingly, it is significance that understanding the molecularpathophysiology of hepatic fibrosis will lead to novel therapeutic strategies andanti-fibrotic drugs.Prunella vulgaris L. is a traditional Chinese medicine. Contain a variety of activechemical ingredients, mainly triterpenoids, steroids, flavonoids, coumarins and othercompounds have anti-virus, anti-tumor, immune regulation, and biological activity.The topic is through to establish the actue liver injury and hepatic fibrosis animalmodel by CCL₄-induced, to get a preliminary understanding the inhibition of totaltriterpenoid of Prunella vulgaris L.（TTP） on rat actue liver injury and hepatic fibrosis.Meanwhile through detect TGF-β/Smad signal transduction Pathway in the key signaltransduction mo1ecules Smad2, Smad3, Smad7, and CYP2E1、p-ERK expression levelchanges in liver, to explore TTP the molecular mechanism of hepatic protective effects.1. Protective effects of TTP on CCL₄-induced actue liver injury modelSixty rats were randomly divided into six groups as follows: control group, CCl4group, TTP （62.5,125and250mg/kg） groups and bifendate （200mg/kg） group. Ratacute liver injury model was induced by peritoneal injection of50%CCl4（2ml/kg,dissolved in corn oil）. Rats in therapeutic groups were pretreated with TTP or bifendatesix days before CCl4was given. Compared with the model group, TTP effectivelyreduced the CCl4-induced elevated serum ALT, AST levels, hepatic MDA content, andrestored hepatic SOD and GSH-Px activities in acute liver injury rats. Furthermore, TTPrestored CYP2E1expression at both protein and mRNA levels in a dose-dependentmanner. These results indicate that TTP had protective and therapeutic effect on rat liver injury, which might be associated with its antioxidant properties and inhibition ofCYP2E1activation.2. Protective effects of hesperidin on CCL₄-induced liver fibrosis modelRat liver fibrosis was induced by50%CCL₄twice a week for12weeks. From the5th week, all the therapeutic groups were treated with the TTP（25,50,100mg/kg） andthe colchicine （0.1mg/kg） respectively for8weeks. Compared with the model group,TTP（25,50,100mg/kg） not only reduced serum content of ALT, AST, HA, LN, PⅢNP,CIV and Hyp, MDA in liver tissue, but also increased SOD activity. Moreover,decreased the α-SMA, procollagen I, Smad2, Smad3mRNA expression and increaseSmad7mRNA expression in liver tissues obviously. Furthermore, TTP reduced theprotein expression of p-ERK. These results showed that TTP had protective effect onhepatic fibrosis.To sum up, TTP has anti-liver injury and anti-liver fibrosis effect, can be effectivein improving liver function, reducing the degree of hepatic injury. Which might beassociated with its antiinflammatory and antioxidant properties and regulateTGF-β/smad signaling pathway.