lithospermic-acid and Disease-Models--Animal

Accumulation of an excess amount of reactive oxygen species (ROS) can cause hepatotoxicity that may result in liver damage. Therefore, development of anti-oxidative agents is needed for reducing liver toxicity. This study investigated the anti-oxidative and hepatoprotective activity of lithospermic acid, a plant-derived polycyclic phenolic carboxylic acid isolated from Salvia miltiorrhiza, on carbon tetrachloride (CCl4)-induced acute liver damage in vitro and in vivo. The results of the DPPH assay indicated that lithospermic acid was a good anti-oxidant. the CCl4-exposed Huh7 cell line exhibited decreased cell viability, increased necrosis and elevated ROS and caspase-3/7 activity. Lithospermic acid significantly attenuated the CCl4-induced oxidative damage in a concentration-dependent manner. The result of an in vivo study with BALB/c mice corresponded with the anti-oxidative activity noted in the in vitro study. Exposure of mice to CCl4 resulted in a greater than 2-fold elevation in serum aspartate transaminase (AST) and alanine transaminase (ALT). levels In addition, CCl4-intoxication led to an over 20% decrease in the level of intracellular hepatic enzymes including superoxide dismutase (SOD) and catalase (CAT) as well as increased lipid peroxidation. Upon histological examination of the CCl4-exposed mice, the mouse livers showed severe hepatic damage with a huge section of necrosis and structural destruction. Pretreatment of mice with lithospermic acid for six days significantly reduced CCl4-induced hepatic oxidative damage, serum AST and ALT. The pretreatment also increased SOD and CAT. The findings suggest that the health status of the liver was improved comparable to the control group after a high-dose treatment with lithospermic acid (100 mg/kg weight). The potential applicability of lithospermic acid as a hepatoprotective agent was demonstrated.

Topics: Animals; Antioxidants; Benzofurans; Carbon Tetrachloride; Cell Line; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Humans; Liver Diseases; Mice; Mice, Inbred BALB C; Superoxide Dismutase

Salviaolate is a group of depside salts isolated from Danshen (a traditional Chinese herbal medicine), with ≥ 85 % of magnesium lithospermate B. This study aims to investigate whether salviaolate is able to protect the rat brain from ischemia/reperfusion injury and the underlying mechanisms. Rats were subjected to 2 h of cerebral ischemia and 24 h of reperfusion to establish an ischemia/reperfusion injury model. The neuroprotective effects of salviaolate at different dosages were evaluated. A dosage (25 mg/kg) was chosen to explore the neuroprotective mechanisms of salviaolate. Neurological function, infarct volume, cellular apoptosis, nicotinamide adenine dinucleotide phosphate-oxidase activity, and H2O2 content were measured. In a nerve cell model of hypoxia/reoxygenation injury, magnesium lithospermate B was applied. Cellular apoptosis, lactate dehydrogenase, nicotinamide adenine dinucleotide phosphate-oxidase activity, and H2O2 content were examined. Ischemia/reperfusion treatment significantly increased the neurological deficit score, infarct volume, and cellular apoptosis accompanied by the elevated nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 content in the rat brains. Administration of salviaolate reduced ischemia/reperfusion-induced cerebral injury in a dose-dependent manner concomitant with a decrease in nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 production. Magnesium lithospermate B (20 mg/kg) and edaravone (6 mg/kg, the positive control) achieved the same beneficial effects as salviaolate did. In the cell experiments, the injury (indicated by apoptosis ratio and lactate dehydrogenase release), nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 content were dramatically increased following hypoxia/reoxygenation, which were attenuated in the presence of magnesium lithospermate B (10(-5) M), VAS2870 (nicotinamide adenine dinucleotide phosphate-oxidase inhibitor), or edaravone (10(-5) M). The results suggest that salviaolate is able to protect the brain from ischemia/reperfusion oxidative injury, which is related to the inhibition of nicotinamide adenine dinucleotide phosphate-oxidase and a reduction of reactive oxygen species production.

Topics: Animals; Antioxidants; Benzofurans; Benzoxazoles; Brain; Brain Ischemia; Cells, Cultured; China; Cinnamates; Depsides; Disease Models, Animal; Drugs, Chinese Herbal; Male; NADPH Oxidases; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Rosmarinic Acid; Salvia miltiorrhiza; Triazoles

Lithospermic acid (LSA) was originally isolated from the roots of Salvia mitiorrhiza, a common herb of oriental medicine. Previous studies demonstrated that LSA has antioxidant effects. In this study, we investigated the in vitro xanthine oxidase (XO) inhibitory activity, and in vivo hypouricemic and anti-inflammatory effects of rats. XO activity was detected by measuring the formation of uric acid or superoxide radicals in the xanthine/xanthine oxidase system. The results showed that LSA inhibited the formation of uric acid and superoxide radicals significantly with an IC50 5.2 and 1.08 microg/ml, respectively, and exhibited competitive inhibition. It was also found that LSA scavenged superoxide radicals directly in the system beta-NADH/PMS and inhibited the production of superoxide in human neutrophils stimulated by PMA and fMLP. LSA was also found to have hypouricemic activity on oxonate-pretreated rats in vivo and have anti-inflammatory effects in a model of gouty arthritis. These results suggested that LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro, and presents hypouricemic and anti-inflammatory actions in vivo.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Benzofurans; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Hyperuricemia; Inflammation; Male; Molecular Conformation; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Oxonic Acid; Rats; Rats, Wistar; Reactive Oxygen Species; Tetradecanoylphorbol Acetate; Uric Acid; Xanthine Oxidase