Paridis Rhizoma Sapoinins attenuates liver fibrosis in rats by regulating the expression of RASAL1/ERK1/2 signal pathway

Ethno-pharmacological relevance: Paridis Rhizoma is a Chinese medicinal herb that has been used in liver disease treatment for thousands of years. Our previous studies found that Paridis Rhizoma saponins (PRS) are the critical components of Paridis Rhizoma which has good liver protection effect. However, the anti-hepatic fibrosis effect and the mechanism of PRS have seldom been reported. Aim of the study: To investigate the potential of PRS in the treatment of experimental liver fibrosis and the underlying mechanism. Materials and methods: The chemical feature fingerprint of PRS was analyzed by UPLC-PDA. A total of 40 Male Sprague-Dawley (SD) rats were randomly divided into the control group, the model group, the PRS high dose group (PRS H) and the PRS low dose group (PRS L) with 10 rats in each group. The model, PRS H and L groups as liver fibrosis models were established with carbon tetrachloride (CCl4) method. PRS H and L groups were adopted PRS (300 and 150 mg/kg d(-1)) treatment since the twelfth week of modeling till the sixteenth week. Pathological changes in hepatic tissue were examined using hematoxylin and eosin (H&E) and MASSON trichrome staining. Immunohistochemical analysis was performed to determine the protein expression of the RASALl. RT-PCR and western blotting were used to detect the expression of ERK1/2 mRNA and protein. Results: Four saponins in PRS were identified from 19 detected chromatographic peaks on UPLC-PDA by comparing to the standard compounds. PRS can improve the degeneration and necrosis of hepatic tissue, reduce the extent of its fibrous hyperplasia according to H&E and MASSON staining detection. As was detected in PRS H and L groups, PRS down-regulated p-ERK1/2 mRNA and RASAL1 protein, and up regulated the level of p-ERK1/2 mRNA and RASAL1 protein. Conclusion: These results demonstrated that PRS can attenuate CCl4-induced liver fibrosis through the regulation of RAS/ERK1/2 signal pathway. 2016 Elsevier Ireland Ltd. All rights reserved.