ABSTRACT
Objective To observe the effect of Acanthus ilicifolius alkaloid A (HBOA) on PI3K/AKT/mTOR/p70S6K signaling pathway in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4), and to explore the mechanism of action of HBOA against liver fibrosis. Methods Rats were randomly divided into normal group, model group, high, medium; and low-dose HBOA groups (100, 50, 25 mg/kg), and colchicine group (0.4 mg/kg). Except for the normal group, the rats in other groups were given with a 50% CCl4 olive oil solution twice a week for 12 weeks to induce a rat model of liver fibrosis. From the ninth week of modeling, the drug-administered group was given the corresponding test drug once daily for 4 weeks. After the experiment, the body mass change and liver index were calculated. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the liver homogenate of each group were detected. The protein expression of p-PI3K, p-Akt, p-mTOR, and p-p70S6K in liver tissue was detected by Western blotting. Results Compared with the model group, the body weight of mice of each drug-administered group was significantly increased, and the liver index, and ALT and AST levels were decreased in liver tissue. In addition, HBOA high and medium-dose groups significantly inhibited the protein expression of p-PI3K, p-Akt, p-mTOR, and p-p70S6K. Conclusion HBOA has a protective effect on hepatic fibrosis rats, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR/p70S6K signaling pathway.
ABSTRACT
Objective:To observe the effect of alkaloid A from Acanthi Ilicifolii Herba seu Radix(AAIA) on liver injury model caused by acetaminophen. Method:Mice were randomly divided into normal group, model group, positive drug group (bifendate, 150 mg·kg-1) and high, medium and low-dose AAIA groups (200, 100, 50 mg·kg-1), with 10 in each group. They were given drugs by gavage for 10 days, and fasted for 8 hours after the last administration. Except the normal group, the other groups were intraperitoneally injected with 275 mg·kg-1 acetaminophen to induce acute liver injury model in mice. Six hours later, blood was taken from the eyeball. The body, liver, spleen, kidney and thymus were weighed, and then the corresponding organ indexes were calculated. The kits were used to detect the contents of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum. The contents of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in liver homogenate were determined by ultraviolet spectrophotometry, and the expressions of extracellular regulated protein kinases (ERK1/2) and phosphorylated extracellular regulatory protein kinase (p-ERK1/2) were determined by Western blot. Result:Compared with the normal group, the liver index, serum AST and ALT levels, the production of NO and iNOS in liver homogenate, the expression of p-ERK1/2 protein in liver of the model group increased significantly (PPConclusion:AAIA may protect mice from drug-induced liver injury by reducing AST and ALT levels, down-regulating the expressions of NO and iNOS, and reducing the expression of protein p-ERK1/2.