ABSTRACT
BACKGROUND AND AIMS: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). METHODS: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-α), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. RESULTS: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-α, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. CONCLUSIONS: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS.
Subject(s)
Drugs, Chinese Herbal/adverse effects , Hepatic Veno-Occlusive Disease/chemically induced , Hepatic Veno-Occlusive Disease/drug therapy , Phytotherapy , Salvia miltiorrhiza , Animals , Disease Models, Animal , Female , MiceABSTRACT
Arginase is upregulated in some tissues under diabetes states. Arginase can compete with nitroxide synthase (NOS) for the common substrate L-arginine and thus increases oxidative stress by NOS uncoupling. We want to analyze whether arginase is upregulated and contribute to oxidative stress in H9c2 cells during high glucose treatment. H9c2 cells were cultured in normal or high glucose DMEM. Arginase activity increased in parallel with increased cell death and oxidative stress. Arginase inhibitor N ω-hydroxy-nor-l-arginine (nor-NOHA) and NOS inhibitor N ω-nitro-l-arginine methyl ester (L-NAME) could reverse these effects. Despite of upregulated NOS activity, NO production was impaired which could be preserved by nor-NOHA, suggesting a decreased substrate availability of NOS due to increased arginase activity. L-arginine supplementation decreased superoxide production while it could not protect cells from death. Upregulated arginase activity in H9c2 treated with high glucose can cause NOS uncoupling and subsequently reactive oxygen species augmentation and cell death. These findings suggest that arginase will be a novel therapeutic target for treatment of diabetic cardiomyopathy.
Subject(s)
Arginase/metabolism , Diabetic Cardiomyopathies/enzymology , Glucose/metabolism , Myocytes, Cardiac/enzymology , Oxidative Stress , Reactive Oxygen Species/metabolism , Animals , Apoptosis , Arginase/antagonists & inhibitors , Arginine/pharmacology , Cell Line , Diabetic Cardiomyopathies/pathology , Enzyme Inhibitors/pharmacology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Nitric Oxide/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Oxidative Stress/drug effects , Rats , Superoxides/metabolism , Time Factors , Up-RegulationABSTRACT
BACKGROUND AND AIM: To investigate the therapeutic effect of ligustrazine on hepatic veno-occlusive disease (HVOD) induced by Gynura segetum and the possible mechanism of it. METHODS: Female Kunming mice (115) were randomly divided into four groups, gavaged with 30 g/kg per day Gynura segetum (group A), 30 g/kg per day Gynura segetum + 100 mg/kg per day ligustrazine (group B), 30 g/kg per day Gynura segetum + 200 mg/kg per day ligustrazine (group C) or 30 mL/kg per day phosphate-buffered saline (PBS) (group D). Thirty days later, all of the mice were killed. Blood samples and livers were harvested. Histological changes were evaluated by light microscopy. Liver function was measured, and the expression of tissue factor (TF), early growth response factor-1 (Egr-1) and nuclear factor-KBp65 (NF-KBp65) were determined by reverse transcription-polymerase chain reaction and Western blot. RESULTS: A total of 24 mice in group A developed HVOD. Compared with the controls, they had increased liver ratio, serum total bilirubin (TBIL), direct bilirubin (DBIL), transaminase and decreased albumin (ALB) (P < 0.05). Administration of ligustrazine improved the clinical signs and biochemistry parameters in a dose-dependent manner. Compared with group A, the expression of TF, Egr-1 and NF-KB p65 decreased in groups B and C (P < 0.05). CONCLUSION: Ligustrazine has a therapeutic effect on HVOD, improving clinical manifestations and liver function. The possible mechanism may be that ligustrazine could reduce the expression of TF by downregulating the expression of transcription factors: Egr-1 and NF-KB p65.