Protective Effect Of Zhizi Bopi Decoction On α-naphthylisothiocyanate Induced Intrahepatic Cholestasis In Rats

The treatment of Chinese medicine on liver diseases has been for thousands of years,Chinese herbal compound in accordance with the principle of "monarch", with whichhas kinds of characteristics such as the multi-target, low side effects, etc. Medicineplays an important role in the international arena which considered to be averypromising treatment in integrative. Zhizi Bopi decoction comes from “Treatise onFebrile Diseases” which composed of Gardenia jasminoides Ellis, Phellodendronchinense Schneid and Glycyrrhiza uralensis Fisch, also has been the treatment ofjaundice for thousands of years. However, the mechanisms involved are still unclear.This study investigated the protective effect and possible mechanisms of Zhizi Bopidecoction on ANIT (α-naphthylisothiocyanate) induced liver injury with intrahepaticcholestasis.Objective To investigate the protective effects of Zhizi Bopi decoction on rats againstα-naphthylisothiocyanaten （ANIT）induced liver injury with cholestasis and analyzedthe possible mechanism.Methods Rats were randomly divided into7groups (N=8): normal group, high doseof the normal group, model group, ZB low, medium and high dose groups (1,2,4g/kg)and Bear deoxycholate acid (You Sifu) group. The rats in each group by1ml/100g dosegavage,2times/d, hold on7d. Normal group and model group were given the same volume of saline. The7th day after4h gavage, in addition to the normal control groupand the high-dose group, and the remaining animals in each group are translated at75mg/kg ANIT olive oil solution orally modeling, modeling the original dose continuedadministration,48h after the ANIT treatment, serum of total bilirubin (TBIL), alkalinephosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST),γ-glutamyltranspeptidase (GGT), liver specimens of superoxide dismutase (SOD),malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-px) weremeasured. To further explore the underlying molecular mechanisms, we measured theexpression of the bile metabolism-related transporters: bile salt export pump (BSEP)，sodium-taurocholate cotrans-porting polypeptide (NTCP) and the enzyme related tooxidative stress: cytochrome P4502E1(CYP2E1) in both mRNA and protein level.Results Zhizi Bopi decoction improved live history with reduced the serum levels ofTBIL, ALP, ALT, AST, GGT, Furthermore, Hepatic MDA activities and contents inliver tissue were significantly reduced, while SOD, GSH, GSH-px activities which weresuppressed by ANIT were significantly elevated in the groups pretreated with ZhiziBopi decoction, a dose-dependently. More than that, Zhizi Bopi decoction was foundincreased the expression of liver NTCP, and decreased the BSEP in ANIT-induced liverinjury with cholestasis. CYP2E1was decreased in accordance with the proteinexpression.Conclusion Zhizi Bopi decoction exerts protective effects against ANIT-induced liverinjury, the mechanisms could be related to transshipment of bile metabolism-relatedtransporters and so as the effect of anti-oxidative damage.