Study on intervention of DCP on MAPK signaling pathway to inhibit inflammatory response and alleviate progression of liver fibrosis in rats / 中国药理学通报

Aim To investigate whether DCP has pro- teetive effeet on 2 ,4-dimethylnitrosamine ( DMN) -induced liver fibrosis rat model and its effect on MAPK signaling pathway.Methods Hats were intraperitoneal ly injected with DMN to establish HF model,and then were randomly divided into five groups, namely model group, colchicine group, DCP low-dose, medium-dose and high-dose groups,and control group.The rats were given DMN continuously for six weeks.Serum was col-lected afterwards to detect biochemical indexes of liver function.HE and Masson staining and immunohisto- chemical experiments were performed on liver tissues.RT-PCR was applied to detect the expression of inflammatory factors.Western blot was used to detect the ex pression of proteins related to MAPK pathway,the preventive effect of DCP on HF was observed, and its in-tervention effect on MAPK pathway was explored.Results The liver function of rats in model group was severely impaired, with obvious hepatocyte damage, inflammatory cell infiltration and increased interstitial fibrosis , suggesting that the preparation of HF model was successful.Conclusions DCP can interfere with MAPK signaling pathway to inhibit the inflammatory response and alleviate the progression of HF in rats.

Protective Effect of Gentiopicroside Against Liver Injury in Mice via TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the mechanism of gentiopicroside （GPS） in preventing acute liver injury induced by carbon tetrachloride （CCl₄） in mice and its effect on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） signaling pathway. Method:Sixty mice were randomly divided into a normal control group， a model group， a silymarin group （150 mg·kg^-1）， and high- （200 mg·kg^-1）， medium- （100 mg·kg^-1）， and low-dose （50 mg·kg^-1） GPS groups， with 10 in each group. The mice in the groups with drug intervention were administered correspondingly by gavage at 10 mL·kg^-1， and those in the normal control group and the model group receive an equal volume of distilled water， once per day. Ten days after administration， mice in the normal control group were subjected to the intraperitoneal injection of peanut oil （10 mL·kg^-1） and those in other groups were injected with peanut oil （10 mL·kg^-1） containing 0.12% CCl₄for the induction of acute liver injury model. After fasting for 16 hours， blood was collected from eyeballs and liver tissues were collected. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of liver tissues. The content or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， alkaline phosphatase （ALP）， total superoxide dismutase （T-SOD）， and <italic>γ</italic>-glutamyl transpeptidase （<italic>γ</italic>-GT） in the serum， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） in liver tissues were determined by biochemistry techniques. The levels of tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， and interleukin-6 （IL-6） in liver tissues were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of TLR4， MyD88， and NF-<italic>κ</italic>B in liver tissues. The expression of phosphorylated NF-<italic>κ</italic>B （p-NF-<italic>κ</italic>B） was detected by immunohistochemistry. Result:Compared with the normal control group， the model group showed increased levels of ALT， AST， ALP， TBIL， <italic>γ</italic>-GT， and MDA （<italic>P</italic><0.01）， and blunted activities of T-SOD and GSH-Px （<italic>P</italic><0.01）. Compared with the model group， the high- and medium-dose GPS groups exhibited declining levels of ALT， AST， ALP， TBIL， <italic>γ</italic>-GT， and MDA （<italic>P</italic><0.05， <italic>P</italic><0.01） and potentiated T-SOD and GSH-Px activities （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the normal control group， the model group displayed elevated levels of TNF-<italic>α</italic>， IL-1<italic>β</italic>， and IL-6 in liver tissues （<italic>P</italic><0.01） and increased protein expression of TLR4， MyD88， and p-NF-<italic>κ</italic>B （<italic>P</italic><0.01）. Compared with the model group， the high- and medium-dose GPS groups showed decreased TNF-<italic>α</italic>， IL-1<italic>β</italic>， and IL-6 content in liver tissues （<italic>P</italic><0.05， <italic>P</italic><0.01） and dwindled TLR4， MyD88， and p-NF-<italic>κ</italic>B protein expression （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:GPS possesses a protective effect on mice with acute liver injury induced by CCl₄， and its mechanism of action may be related to the regulation of TLR4/MyD88/NF-<italic>κ</italic>B signaling pathway and inhibition of oxidative stress.