Intervention effect and mechanism of Huangqi Xiayuxue Decoction on hepatic fibrosis induced by carbon tetrachloride in mice
Objective It is to investigate the intervention effect and potential mechanisms of the combined decoction of Huangqi Decoction and Xiayuxue Decoction(Huangqi Xiayuxue Decoction)on carbon tetrachloride-induced hepatic fibrosis in mice based on NOD-like receptor pyrin domain containing 3(NLRP3)/Caspase-1/interleukin-1(IL-1β)pathway.Methods Seventy-five 6-week-old C57BL/6 mice were selected,in which15 mice were randomly selected as normal group,and the remaining mice were injected intraperitoneally with 15%CCl4 olive oil solution(2 mL/kg body weight,3 times per week)to establish the models.One week later,the modeled mice were randomly subdivided into model group,Huangqi Decoction group,Xiayuxue Decoction group,and Huangqi Xiayuxue Decoction group,with 15 mice in each group.While continuing CCl4 modeling,the treatment groups were administered the corresponding drugs daily by gavage,and the control and model groups were given an equivalent volume of double-distilled water by gavage,all treated for 5 weeks.At the end of 6 weeks,the mice were euthanized,the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),tumor necrosis factor-α(TNF-α)and interleukin 6(IL-6)were detected,the liver tissue inflammation and colla-gen deposition were observed by HE staining and Sirius Red staining,the contents of superoxide dismutase(SOD),malon-dialdehyde(MDA)and hydroxyproline(Hyp)in liver tissues were detected by assay kits,the protein expressions of liver tissue collagen proliferation markers such as fibronectin(FN),type Ⅰ collagen(Col I),alpha-smooth muscle actin(α-SMA),and NLRP3,Caspase-1 and IL-1β were detected by Western blot method.Results Huangqi Decoction,Xiayuxue Decoction and Huangqi Xiayuxue Decoction could all significantly reduce indexes of liver function and serum levels of in-flammatory cytokines in model mice with hepatic fibrosis,they also could increase the activity of SOD and decrease contents of MDA and Hyp in liver tissue,improve liver tissue inflammatory injury and collagen deposition,and downregulate the ex-pressions of FN,Col I,and α-SMA in liver tissue,the effects were further enhanced by Huangqi Xiayuxue Decoction com-pared with Huangqi Decoction or Xiayuxue Decoction used alone,particularly in terms of collagen deposition and Hyp in liver tissue,the differences were all statistically significant(all P<0.05).Huangqi Xiayuxue Decoction could also down-regulate the protein expression levels of NLRP3,Caspase-1,and IL-1β in liver tissue.Conclusion Huangqi Xiayuxue De-coction can effectively improve liver function of mice with CCl4-induced hepatic fibrosis,and could alleviate liver tissue in-flammation and reduce collagen deposition,and its preventive and therapeutic effects on hepatic fibrosis were more signifi-cant that those of Huangqi Decoction and Xiayuxue Decoction.Its mechanism is related to regulating NLRP3/Caspase-1/IL-1β pathway to inhibit inflammatory responses and oxidative stress.
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