| Objective: To study the differential hepatotoxicity of raw polygonum multiflorum and polygonum multiflorum praeparata and explore its underlying mechanism.Methods: 1.C57BL/6 mice were divided into three groups,namely control group,RPM group and PMP group.Control group:(CON): gavaged with saline for 30 days;RPM group: gavaged with RPM for 30 days;PMP group : gavaged with processed PMP for 30 days.The sera were collected for biochemical analysis and HE staining was applied to examine the morphological alternation of the liver.2.we treated L02 cells with 5mg / m L of RPM or PMP.The CCK8 and Ed U assays were utilized to observe the viability and proliferation of L02 cells.3.RNA sequencing was performed to explore the expression profile of L02 cells.Western blot was performed to detect the expression level of ferroptosis-related protein.Flow cytometry was used to evaluate ROS accumulation.Results: 1.A significant elevation in serum ALT,AST and TBIL levels was investigated in the RMP group,while no significant differences were observed in the PMP group,compared to that of the CON group.HE staining showed punctate necrosis,inflammatory cell infiltration and structural destruction can be observed in the RPM group,which can be significantly attenuated after processing.2.In addition,we also found RPM could decrease the viability and proliferation capacity of L02 cells,which can be reversed by ferroptosis inhibitor.3.RNA sequencing data revealed the adverse effect of PM exerted on the liver is closely associated with ferroptosis.Western blot assay uncovered the protein level of GPX4,HO-1 and FTL was sharply decreased,while the ROS content was dramatically elevated in L02 cells treated with RPM,which can be partially restored after processing.Conclusion: Our results revealed ferroptosis is the potential mechanism of differential adverse effects of RPM and PMP exerted on the liver,thus providing new insights into PM-induced hepatotoxicity. |
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