ABSTRACT
To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.
ABSTRACT
Objective: To investigate the protective effect of Liuweiwuling Tablets of Polygonum multiflorum (PM)-induced idiosyncratic hepatotoxicity. Methods: Eighty Sprague-Dawley (SD) rats were randomly divided into control group, LPS group, PM group, LPS + PM group, LPS + PM + Liuweiwuling Tablets low, medium, and high dose (0.4, 0.8, and1.6 g/kg) groups, and LPS + PM + positive drug Biphenyl group (2 mg/kg). All groups were orally given Liuweiwuling Tablets and Biphenyl once daily for consecutive 2 d according to the different dosages. On day 3, except the normal group and LPS group oral administration of distilled water, all groups were given PM (crude drug 2.16 g/kg), 3 h after the group by the tail vein injection LPS (2.8 mg/kg) according to the different dosage; After 7 h, the rats were anesthetized with sodium pentobarbital, and the inferior vena cava was used to collect blood and liver tissue samples were collected. HE staining was used to observe the pathological changes of liver tissue, and the contents of ALT, AST, TNF-α, IL-1β, IL-6, and IFN-γ in rat plasma were determined. TUNEL assay analyzed hepatocyte apoptosis, and immunohistochemical staining was performed to detect the liver tissue expression activity of NF-κB p65. Results: Liuweiwuling Tablets could decrease ALT and AST levels of PM-induced idiosyncratic liver injury rat plasma, reduce liver pathological injury and hepatocyte apoptosis, inhibit the expression of NF-κB p65, and decrease plasma TNF-α and other inflammatory cytokines. Conclusion: Liuweiwuling Tablets can reduce inflammation through the inhibition of NF-κB signaling pathway, and prevent of PM induced idiosyncratic liver injury.
ABSTRACT
The protective action and the relevant mechanism of Liuwei Wuling tablet on acute alcoholic hepatic injury in mice were investigated. All the C57BL/6 mice were divided randomly into 7 groups including blank, model, bifendate (150 mg•kg⁻¹, positive control) and experimental groups consisted of extremely low dose (0.1 g•kg⁻¹), low (0.5 g•kg⁻¹), upper (4 g•kg⁻¹) and high dose (8 g•kg⁻¹) of Liuwei Wuling tablet groups. The acute liver injury model was induced by modified method that the model, positive control and experimental groups were orally administrated 56% alcohol (6 g•kg⁻¹) twice at 12 hour intervals on the fifth day after drugs administration. After 12 hours, the mice were sacrificed to contribute blood and liver for biochemical and histological examinations. Compared with the model, the activities of ALT and AST in serum decreased significantly in different Liuwei Wuling tablet groups. Meanwhile, in liver tissue, the levels of TG, MDA, TNF-α and IL-1β reduced obviously while the GSH and SOD activities showed markedly increase with a dose-dependent manner. Correspondingly, the microscopically pathological differences of the liver tissue observed by HE and oil red O staining indicated that the liver cell swelling, hydropic degeneration and lipid droplets formation induced by alcohol were significantly improved, which suggested the Liuwei Wuling tablet can reduce the liver injure. In conclusion, the Liuwei Wuling tablet had the protective effect on acute alcoholic hepatic injury which maybe depended on the mechanism of relieving lipid peroxidation, elevating antioxidant enzymes activity, inhibiting oxidative stress and reducing inflammation factors expression.
ABSTRACT
To investigate the protective effects of oxymatrine (OMT) against H2O2-induced damage in L02 cells and research the mechanism,L02 cells were used as the research object. The oxidative stress model of L02 was established by hydrogen peroxide (H2O2). CCK-8 was used to detect the cell activation of L02 cells treated by different OMT. FCM (flow cytometry) assay was used to evaluate the cell proliferation of L02 cells treated by OMT. The apoptosis of L02 cells was detected using Annexin-V/7-AAD apoptosis detection kit. The level of ROS was detected by DCFH-DA fluorescence probe. The GSH-PX and SOD were detected by micro plate and colorimetric method. Results showed that when the concentration of OMT is between 6.25 and 100 mg•L⁻¹, it could promote the production of NADPH and strengthen the activity of GSH-PX and SOD to get rid of the ROS to protect the L02 cell from the apoptosis of L02 cell induced by H2O2.
ABSTRACT
This paper was aimed to investigate the protective effects of luteolin (Lut) against acetaminophen（APAP）-induced damage in L02 liver cells. CCK-8 was used to detect the cell activation of L02 cells treated by different Lut. The concentration and time of APAP induced L02 cell damage was screened. The effect of Lut on APAP induced apoptosis of L02 cells was detected by cell morphological observation, CCK-8 assay and flow cytometry. The contents of MDA, GSH and SOD activity in cell supernatant were detected by colorimetric assay. The expression of apoptosis-related genes Bax, Bcl-2 and caspase-3 was detected by RT-PCR. The results showed that Lut in 2.5-40 μmol•L⁻¹ range does not affect the activity of L02 cells; 12 mmol•L⁻¹ APAP incubated with L02 cell 12 h to establish damage model. Compared with the model group, the cell status of Lut group was significantly improved, the cell body was increased, the adherence ability was recovered, and the apoptosis rate was obviously decreased. MDA content decreased significantly (P<0.05, P<0.01), GSH and SOD activity significantly increased (P<0.05, P<0.01), at the same time, it could up-regulate expression of Bcl-2 mRNA and down-regulate the expression of Bax and caspase-3 mRNA. In conclusion,Lut has protective effect on APAP induced L02 cell injury, and its mechanism may be related to the reduction of oxidative stress and inhibition of apoptosis.