OBJECTIVETo study the variation Laws of content of danshensu accelerated in control and in danshen injection in order to provide reference for stability investigation of danshensu.

METHODThe tests was carried out by classic isothermal method and the content of danshensu was determined by HPLC.

RESULTThe contents of danshensu in accelerated tests increase in control and decrease in danshen injection respectively.

CONCLUSIONThe component of phenic acidity would be hydrolyzed to become danshensu in the accelerated tests. Much attention should be paid to the unusual increase when studies of danshen preparations are carried out.

Chromatography, High Pressure Liquid ; Drug Stability ; Hydrolysis ; Hydroxybenzoates ; chemistry ; Injections ; Lactates ; administration & dosage ; analysis ; chemistry ; Temperature

OBJECTIVETo develop a HPLC method for determination of the concentration of Danshensu in rat plasma and undertake comparative pharmacokinetic study of sodium danshensu and Salvia miltiorrhiza injection in rat as well as to assess the effect of other components of Salvia miltiorrhiza injection on the pharmacokinetics of Danshensu.

METHODRats received an iv. infusion of sodium Danshensu or S. miltiorrhiza injection (equal to Danshensu 30 mg x kg(-1)). Blood samples were collected from carotid artery. Plasma concentration of Danshensu extracted with perchloric acid was measured. The pharmacokinetic parameters were calculated with DAS2.0 software.

RESULTA good linear relationship of Danshensu was obtained from the range of 0.5 to 80.0 mg x L(-1), and the lowest limit of determination was 0.2 mg x L(-1). The plasma concentration time curves of Danshensu were best fitted with two-compartment models for Danshensu itself and for Salvia miltiorrhiza injection as well. The pharmacokinetic parameters such as t1/2alpha, AUC, CL had significant differences.

CONCLUSIONThe concomitant components in Salvia miltiorrhiza injection influence the pharmacokinetic properties of Danshensu and speed up its disposition and elimination.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Lactates ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

As a novel targeting drug delivery system, acid-sensitive micelles have many advantages, such as increasing solubility of lipophilic drugs, acid-sensitive release, high drug loading, etc. They can load drugs though non-covalent encapsulation and covalent conjugation methods. In tumor tissues, drugs are released quickly from the depolymerized micelles with lipophilic copolymer protonation or lypohydrophilic copolymer hydrolysis and covalent conjugated drugs are released when the acid-sensitive covalent linkage breaks. This review mainly advances acid-sensitive micelles for the tumor targeting drug delivery systems from drug-loaded methods and release mechanisms.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Humans ; Hydrogen-Ion Concentration ; Lactates ; chemistry ; Micelles ; Paclitaxel ; administration & dosage ; pharmacology ; Polyethylene Glycols ; chemistry ; Polymers

Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.
Administration, Intravenous ; Animals ; Caffeic Acids ; pharmacokinetics ; Chromatography, Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Lactates ; pharmacokinetics ; Macaca mulatta ; Mass Spectrometry ; Plant Roots ; chemistry ; Salvia miltiorrhiza ; chemistry

To study the rheological properties of sucrose acetate isobutyrate (SAIB) in situ gel and the influencing factors. Measurements of shear stress and viscosity were carried out at different shear rate. The rheological properties of SAIB solution were similar to those of Newtonian fluid. The factors such as the type of solvent, concentration, additive, drug and temperature had effect on the rheological properties. Ethanol was a suitable solvent compared with ethyl lactate and N-methylpyrrolidone (NMP). The solution viscosity of SAIB was reduced from 1.29 to 0.11 Pa x s with only increasing the content of ethanol from 10% to 20%. Polylactic acid (PLA) and risperidone could increase the intermolecular force and viscosity. However, adding 10% (w/w) PLA, the initial release of risperidone was reduced from 20.2% to 3.5%. The solution viscosity reduced significantly by stepping up the temperature. The results obtained support the using of SAIB is satisfactorily injectable in situ gel formulation.
Antipsychotic Agents ; administration & dosage ; Delayed-Action Preparations ; Drug Carriers ; Ethanol ; Lactates ; Lactic Acid ; Polyesters ; Polymers ; Pyrrolidinones ; Rheology ; Risperidone ; administration & dosage ; Solvents ; Sucrose ; administration & dosage ; analogs & derivatives ; chemistry ; Temperature ; Viscosity

OBJECTIVETo investigate the influence of Shi herb (Santalum album, SA) to the tissue distribution of danshensu (DSS) which is the main hydrosoluble component of Jun herb (Salvia miltiorrhiza, SM) in rabbits by HPLC.

METHODRabbits were oral administrated decoction of SM and SM-SA, respectively. Perchloric acid (10%) was used to precipitate the tissue samples of rabbits heart, brain, liver, kidney, acetic ether was used to extracte supernatant, and the internal standard was p-hydroxybenzoic acid. The content of DSS of SM in tissues was detected.

RESULTThe content of DSS reached the highest point close to 50 min in the mentioned tissues. Before and after co-administration, the sequences of average concentration of DSS in tissues were C(kidney) > C(heart) > C(brain) > C(liver) and C(kidney) > C(liver) > C(brain) > C(heart) respectively. Compared with SM administrated singly, the content of DSS in every tissues of co-administration was higher.

CONCLUSIONIn Danshenyin Formulae, SA can increase concentration of DSS in target tissues significantly, and therefore therapeutic effect of SM for cardiovascular disease is raised.

Animals ; Brain ; drug effects ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Heart ; drug effects ; Kidney ; drug effects ; Lactates ; administration & dosage ; analysis ; pharmacokinetics ; Liver ; drug effects ; Rabbits ; Santalum ; chemistry

To develop a LC-MS/MS method for the determination of protocatechuic acid, protocatechuic aldehyde, salvianolic acid A, salvianolic acid B, cryptotanshinone and tanshinone II(A) in rat plasma and brain. The plasma and brain samples were precipitated with ethyl acetate, then were separated on an Agilent eclipse plus-C18 column (2.1 mm x 50 mm, 3.5 microm) using acetonitrile (consisting of 0.1% formic acid) and water (consisting of 0.1% formic acid) as mobile phase in gradient elution mode. The mass spectrometer was operated under both positive and negative ion mode with the ESI source, and the detection was performed by MRM. The transition of 154.3/153.1 m/z for protocatechuic acid, 137.3/108 m/z for protocatechuic aldehyde, 493.0/295.2 m/z for Salvianolic acid A, 718.0/520.0 m/z for salvianolic acid B, 321.4/152.3 m/z for chloramphenicol, 297.4/254.3 m/z for cryptotanshinone, 295.5/249.3 m/z for tanshinone II(A) and 285.2/154.0 m/z for Diazepam. The calibration curves in the range of 0.625-1 000 microg x L(-1) for protocatechuic acid and protocatechuic aldehyde, 1.25-1 000 microg x L(-1) for salvianolic acid A, 2.5-1 000 microg x L(-1) for salvianolic acid B, 0.15-1 000 microg x L(-1) for cryptotanshinone, 0.625-1 000 microg x L(-1) for tanshinone II(A) are with good linearityin rat plasma and brain. The analysis method is sensitive, simple, and suitable enough to be applied in the pharmacokinetic study of the 6 main components. Animal testing gives the lgBB of the drugs and further studies of the 6 components cross the blood-brain barrier can be carried out.
Animals ; Benzaldehydes ; administration & dosage ; blood ; pharmacokinetics ; Benzofurans ; administration & dosage ; blood ; pharmacokinetics ; Blood-Brain Barrier ; metabolism ; Brain ; metabolism ; Caffeic Acids ; administration & dosage ; blood ; pharmacokinetics ; Catechols ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, Liquid ; methods ; Diterpenes, Abietane ; administration & dosage ; blood ; pharmacokinetics ; Hydroxybenzoates ; administration & dosage ; blood ; pharmacokinetics ; Injections, Intravenous ; Lactates ; administration & dosage ; blood ; pharmacokinetics ; Phenanthrenes ; administration & dosage ; blood ; pharmacokinetics ; Plant Preparations ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry ; Tandem Mass Spectrometry ; methods

OBJECTIVEAn RP-HPLC procedure was established for the determination of danshensu and protocatechuic aldehyde in Guanxinning injection powder.

METHODAn RP-HPLC analytical procedure was developed using Hypersil ODS2 C18 column (4.6 mm x 250 mm, 5 microm) with methanol-0.5% glaceal acetic acid (4.5:95.5) as mobile phase, and a wavelength of 280 nm for UV detection.

RESULTThe linear range was 3.004-45.06 microg x m(L-1) (r = 0.999 5, n = 6) for danshensu, and 0.300-4.509 microg x mL(-1) (r = 0.999 3, n = 6) for protocatechuic aldehyde. The average recoveries were 99.1% and 97.9%, respectively.

CONCLUSIONThe method was stable, accurate, and reproducible, and can be used for the quality control of Guanxinning injection powder.

Benzaldehydes ; analysis ; Catechols ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; Injections ; Lactates ; analysis ; Ligusticum ; chemistry ; Plants, Medicinal ; chemistry ; Powders ; Quality Control ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry

The correlation between muscle glycogen content and physical performance in mice was evaluated by investigating whether an increase in glycogen content in skeletal muscle with insulin administration can improve the physical performance without other effects of exercise. Albino rats(group I) were divided into two groups, i.e., insulin and saline administered group. The former experimental group was treated with protamine zinc insulin(15U/kg/day) subcutaneously for two weeks to increase the content of the muscle glycogen and the latter control group with saline. Mice (group II) were also divided into insulin treated and control groups and both groups were subjected to running exercise on an animal treadmill up to point of exhaustion once every day. After two weeks of insulin treatment, the muscle glycogen content, the maximal running time and the maximal swimming time were measured in non-exercised group I. In group II, after 12 days of insulin and saline administration, the muscle glycogen content, the maximal running time, concentrations of lactate and pyruvate in the blood were measured before and after the maximal exhaustive running. The results were summarized as follows. In group I, the muscle glycogen content, the maximal running time and the maximal swimming time of the insulin administered group were significantly greater of the control groups. In group II, the maximal running time was significantly greater(P < 0.01) in the experimental group than of the control group, while the muscle glycogen content revealed no significant difference between the two groups. On the other hand, lactate concentration and lactate/pyruvate ratios in the blood were significantly lower in the experimental group than those of the control groups. From the above results, it may be concluded that the elevation of muscle glycogen content alone by insulin treatment without any previous physical training can improve physical performance of rats. And insulin was also found to improve physical performance even in experimental animals which had been subjected to a longterm of exercise.
Anaerobiosis/drug effects* ; Animal ; Blood Glucose/analysis ; Body Weight ; Exertion/drug effects* ; Glycogen/analysis* ; Injections, Subcutaneous* ; Insulin/administration & dosage ; Insulin/pharmacology* ; Lactates/blood ; Male ; Metabolism/drug effects* ; Mice ; Muscles/analysis* ; Pyruvates/blood ; Rats

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Blood-Brain Barrier ; drug effects ; enzymology ; immunology ; Brain ; Brain Ischemia ; drug therapy ; enzymology ; genetics ; Caffeic Acids ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Lactates ; administration & dosage ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; genetics ; immunology ; prevention & control ; Salvia miltiorrhiza ; chemistry ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transcription Factor RelA ; genetics ; immunology