Objective: To investigate the inhibitory effect of piperine on liver receptor homolog-1(LRH-1) related signal pathway in liver tissues of mice with cholesterol gallston. Method: A total of 90 male C57BL/6J mice were randomly divided into six groups

namely normal group

model group

ursodeoxycholic acid (UDCA)group (90 mg·kg-1)

and low-dose

middle-dose

high-dose piperine groups(20

40

60 mg·kg-1 respectively)

15 mice in each group. The mice received intragastrical administration for 4 weeks. Except for the normal group

the mice of other groups were fed with high-fat diet containing 2% cholesterol for 4 weeks to establish cholesterol gallston models. The stone formation was observed with naked eyes; gallbladder volume was measured

and the levels of serum total cholesterol (TC)

triglyceride (TG)

low-density lipoprotein cholesterol (LDL-C)

and high-density lipoprotein cholesterol (HDL-C) were detected. The protein expression levels of LRH-1

scavenger receptor BⅠ(SRBI)

ATP binding cassette transport-G5(ABCG5)

ABCG8 in liver tissues of each group were detected by Western blot

and the mRNA expression levels of LRH-1

SRBI

ABCG5 and ABCG8 in liver tissues of each group were detected by real time polymerase chain reaction (Real-time PCR). Result: As compared with the normal group

the rate of stone formation in the model group was significantly increased (P<0.05); the volume of gallbladder was increased significantly (P<0.05); the contents of TC

TG and LDL-C in serum were increased significantly(P<0.05); the content of HDL-C in serum was decreased significantly(P<0.05)

and the protein and mRNA expression levels of LRH-1

SRBI

ABCG5 and ABCG8 in liver tissues were increased significantly (P<0.05). As compared with the model group

the rate of stone formation in ursodeoxycholic acid group and piperine medium and high dose groups was significantly lower (P<0.05); the volume of gallbladder was decreased significantly(P<0.05); the contents of TC

TG and LDL-C in serum were decreased significantly (P<0.05); the content of HDL-C in serum was increased significantly(P<0.05); the protein and mRNA expression levels of LRH-1

SRBI

ABCG5 and ABCG8 in liver tissue were decreased significantly (P<0.05). Conclusion: Medium and high dose (40

60 mg·kg-1) piperine can inhibit the formation of cholesterol gallstones in the gallbladder of C57BL/6 mice induced by high cholesterol diet

which may be related to the improvement of lipid metabolism abnormality and inhibition of the expression of LRH-1/SRBI and LRH-1/ABCG5/ABCG8 signaling pathways in the liver tissue; moreover

piperine high dose group had better effects than piperine medium dose group.