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
Chinese Journal of Experimental Traditional Medical Formulae
; (24): 76-83, 2021.
Article
in Zh
| WPRIM
| ID: wpr-905929
Responsible library:
WPRO
ABSTRACT
Objective:To explore the mechanism of gentiopicroside (GPS) in preventing acute liver injury induced by carbon tetrachloride (CCl<sub>4</sub>) 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<sup>-1</sup>), and high- (200 mg·kg<sup>-1</sup>), medium- (100 mg·kg<sup>-1</sup>), and low-dose (50 mg·kg<sup>-1</sup>) GPS groups, with 10 in each group. The mice in the groups with drug intervention were administered correspondingly by gavage at 10 mL·kg<sup>-1</sup>, 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<sup>-1</sup>) and those in other groups were injected with peanut oil (10 mL·kg<sup>-1</sup>) containing 0.12% CCl<sub>4 </sub>for 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 CCl<sub>4</sub>, 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.
Full text:
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Index:
WPRIM
Type of study:
Prognostic_studies
Language:
Zh
Journal:
Chinese Journal of Experimental Traditional Medical Formulae
Year:
2021
Type:
Article