ABSTRACT
BACKGROUND: The brain is secondarily harmed by pathological, physiological, and biological reactions that are caused by traumatic brain injury (TBI). Rhein, a significant composition of Rhubarb, is a well-known traditional Chinese treatment method and has a strong oxidation-resisting characteristic, but Rhein's mechanism remains unclear. METHODS: This study aimed to identify Rhein in the brain tissues of TBI model of rats, and confirm whether Rhein induced an antioxidative effect similar to its parent medicine, Rhubarb. First, the ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was applied to identify Rhein in the brain tissue of the controlled cortical impact (CCI) rats after intra-gastric administration of Rhubarb. Further, for the purpose of calculating the oxidant stress of the CCI rats, the malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione disulfide (GSSG), as well as the proportion of glutathione (GSH)/GSSG were measured in the brain tissues. RESULTS: The results showed that Rhein was absorbed in the brain tissues of CCI rats. Rhubarb and rhein elevated the SOD, CAT activities, GSH level, and GSH/GSSG ratio, and diminished the MDA and GSSG levels. CONCLUSION: The data demonstrated that Rhubarb and Rhein had the potential to be used as a neuroprotective drug for TBI, and that Rhein induced an antioxidative effect similar to its parent medicine, Rhubarb.
Subject(s)
Brain Injuries, Traumatic/metabolism , Brain/drug effects , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Rheum/chemistry , Animals , Brain/enzymology , Brain/metabolism , Chromatography, High Pressure Liquid , Disease Models, Animal , Male , Neuroprotective Agents/chemistry , Plant Extracts/chemistry , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry/methodsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort), known as Chuanxiong in Chinese, has been used for treating cardiovascular diseases for centuries. Chuanxiong is a classical activating blood circulation herb in the treatment of thromboembolism heart diseases. Warfarin often combines with herbal prescriptions containing Chuanxiong in China. AIM OF THE STUDY: The herb-drug interaction involving enterohepatic circulation process remains unclear. This study aimed to elucidate the effects of Chuanxiong Rhizoma on the pharmacokinetics of warfarin in rats after biliary drainage. MATERIALS AND METHODS: Thirty-two rats were randomly divided into four groups: WN (healthy rats after the gastric-administration of 0.5mg/kg warfarin sodium), WO (a rat model of biliary drainage after the gastric-administration of 0.5mg/kg warfarin sodium), WCN (healthy rats after the gastric-administration of 0.5mg/kg warfarin sodium and 10g/kg Chuanxiong decoction), and WCO (a rat model of biliary drainage after the gastric-administration of 0.5mg/kg warfarin sodium and 10g/kg Chuanxiong decoction). The levels of warfarin and internal standard were quantified by LC-MS/MS. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. RESULTS: The established LC-MS/MS method was specific, precise and rapid. The pharmacokinetic parameters showed a significant difference between the WN and WO groups. There were significant differences in the area under the curve (AUC0-t), peak concentration (Cmax), total plasma clearance (CLz/F) and mean residence time (MRT0-t) between the WCO and WCN groups; the AUC0-t of warfarin in the WCN group was 2.42 times than that of the WN group (p<0.01); the WCO group displayed a decreased to 61.6% in the Cmax compared the WO group (p<0.01). CONCLUSION: Biliary drainage significantly influenced the disposition of warfarin, and Chuanxiong significantly affected the warfarin disposition in rat plasma.
Subject(s)
Anticoagulants/pharmacokinetics , Herb-Drug Interactions , Ligusticum , Rhizome , Warfarin/pharmacokinetics , Animals , Biliary Tract , Drainage , RatsABSTRACT
According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA) is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN): healthy rats after the administration of warfarin sodium, Group 2 (WO): a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN): healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO): a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography-tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0- t ) and peak plasma concentration (C max), respectively, whereas time to C max (T max) was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0- t and C max, respectively; the delay in T max between the WN and WFN groups (mean, from 132-432 minutes) was significantly different; the mean retention time from 0 to time (MRT0- t ) between the WO and WFO groups (mean, from 718.31-606.13 minutes) also showed a significant difference. Enterohepatic circulation markedly influences the disposition of warfarin in rats, and FA significantly affected the warfarin disposition in rat plasma.
Subject(s)
Coumaric Acids/chemistry , Drugs, Chinese Herbal/analysis , Enterohepatic Circulation/drug effects , Tandem Mass Spectrometry/methods , Warfarin/analysis , Warfarin/pharmacokinetics , Administration, Oral , Animals , Coumaric Acids/pharmacology , Drainage , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , Humans , Rats , Warfarin/chemistryABSTRACT
A simple, novel, specific, rapid and reproducible ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for the determination of hydroxysafflor yellow A (HSYA) in biological fluids (plasma, urine and cerebrospinal fluid) of patients with traumatic brain injury after intravenous injection of Xuebijing (XBJ). Liquid-liquid extraction was performed, and separation was carried out on an Acquity UPLC™ BEH C18 column, with gradient elution using a mobile phase composed of methanol and 0.1% formic acid at a flow rate of 0.3 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization was used for the detection of HSYA. The mass transition followed was m/z 611.0 â 491. The retention time was less than 3.0 min. The calibration curve was linear in the concentration range from 2 to 6125 ng/mL for cerebrospinal fluid, plasma and urine. The intra- and inter-day precisions were <10%, and the relative standard deviation of recovery was <15% for HSYA in biological matrices. The method was successfully applied for the first time to quantify HSYA in the biological fluids (especially in cerebrospinal fluid) of patients with traumatic brain injury following intravenous administration of XBJ.
Subject(s)
Brain Injuries/drug therapy , Brain Injuries/metabolism , Chalcone/analogs & derivatives , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/therapeutic use , Quinones/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Chalcone/analysis , Chalcone/chemistry , Chalcone/pharmacokinetics , Drugs, Chinese Herbal/pharmacokinetics , Humans , Injections, Intravenous , Linear Models , Quinones/chemistry , Quinones/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Tandem Mass Spectrometry/methodsABSTRACT
The quality assessment and control of traditional Chinese medicines (TCM) has received a great deal of attention worldwide with its tremendous increasing use. Chromatographic fingerprinting is thought to be a good approach for this task and has been used for the quality assessment and control of many herbal medicines. However, there are only a few reports on the quality control of TCM preparation by chromatographic fingerprinting. In the present work, gas chromatography-mass spectrometry (GC-MS) combined with chemometric methods were used for the chromatographic fingerprint analysis and characterization of Shengui hair-growth tincture (SGHGT), which is a complex TCM prescription made from 9 herbs. Thirteen "common peaks" were identified by MS and a comparison of retention indices. The software "The Traditional Chinese Medicine Quality Control System 1.0" (TCMQCS, developed by Research Center of Modernization of Chinese Herbal Medicine, Central South University) was used to evaluate the similarities. Principal component analysis (PCA) was used for the classification of 23 batches of SGHGT samples provided by Hunan Fusheng Hairgrowth Pharmaceutical Factory. The 23 batches of samples made in different years had similar GC-MS fingerprints. Four clusters were obtained from PCA treatment according to their production year. The proposed method was validated in precision and repeatability through the calculation of relative retention times and relative peak areas of the 13 common compounds to the reference compound eugenol. The result indicated that the method is feasible and applicable for the quality control of SGHGT. SUPPORTING INFORMATION available online at http://www.thieme-connect.de/ejournals/toc/plantamedica.