lithospermic-acid and Brain-Ischemia

The quality of Chinese medicine (CM) has being an active and challenging research area for CM. Prof. Chang-Xiao Liu et al first proposed the concept of quality marker (Q-Marker) for the quality evaluation and control on CM. This article describe the exploratory studies of Q-Marker in salvianolic acids for injection (SAI) based on this new concept.. This study was designed to screen Q-Marker of SAI and establish its quality control method based on the concept of CM Q-Marker.. Based on the concept of CM Q-Marker, the SAI was investigated for the identification of chemical components and their sources. The pharmacological effects on cerebral ischemia and reperfusion induced injury in rats were also investigated. Furthermore, the target cell extracts and pharmacokinetic studies were conducted to screen Q-Markers. Finally, the fingerprints and determination based on Q-Markers were established to assess the quality of SAI more effectively.. Overall, 20 constituents in SAI were identified. It was found that salvianolic acid B (SA-B), rosmarinic acid (RA), lithospermic acid (LA), salvianolic acid D (SA-D) and salvianolic acid Y (SA-Y) are major chemical components of SAI. Based on chemical components identifications, analysis of their sources, target cell extracts and pharmacokinetic studies, four phenolic acids, namely SA-B, RA, LA and SA-D, were screened and determined as effective Q-Markers of SAI.. This study demonstrated that the described method is a powerful approach for detecting Q-Markers, which can be used as control index for the quality assessment of CM.

Topics: Alkenes; Animals; Benzofurans; Biomarkers; Brain; Brain Ischemia; Cell Line; Cinnamates; Depsides; Drugs, Chinese Herbal; Endothelium, Vascular; Injections; Interleukin-1; Interleukin-6; Male; Polyphenols; Quality Control; Rats, Sprague-Dawley; Rosmarinic Acid; 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