BackgroundThe 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.MethodsThis 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.ResultsThe 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.ConclusionThe 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.

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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 → 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.

The aim of this study was to elucidate the effects of warfarin on senkyunolide I in a rat model of biliary drainage after oral administration Chuanxiong extract based on pharmacokinetics. Thirty-two rats were randomly divided into four groups: CN, healthy rats after a single administration of Chuanxiong; CO, rats with biliary drainage after a single administration of Chuanxiong; WCN, healthy rats after the administration of Chuanxiong and warfarin; WCO, rats with biliary drainage after the administration of Chuanxiong and warfarin. A series of blood samples were collected at different time points before and after oral administration. An ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method for quantification of the main components of Chuanxiong and methyclothiazide (internal standard) have been established. The validated method was successfully applied to a comparative pharmacokinetics study. After calculated by the DAS 2.1.1 software, the pharmacokinetics parameters of senkyunolide I showed a significant difference between the CN and CO groups, the AUC0−t, and Cmax of CO group increased by 5.45, 4.02 folds, respectively. There was a significant difference between the WCO and WCN groups, the Tmax of WCO group prolonged 67%; compared to the CN group, the AUC0−t, and Cmax of WCN group raised 4.84, 3.49 folds, respectively; the Tmax and Cmax between the CO and WCO groups also showed a significant difference. The drug warfarin significantly affected the senkyunolide I disposition, which partly due to its enterohepatic circulation process in rat plasma after oral administration of Chuanxiong. The present study highlights an urgent evidence for drug-herb interactions.

Damage of blood-brain barrier is a common result of traumatic brain injury. This damage can open the blood-brain barrier and allow drug passage. An ultraperformance liquid chromatography with tandem mass spectrometry method was established to determine the concentration of rhein in the biofluids (plasma and cerebrospinal fluid) of patients with a compromised blood-brain barrier following traumatic brain injury after rhubarb administration. Furthermore, the pharmacokinetic profiles were analyzed. A triple-quadruple tandem mass spectrometer with electrospray ionization was used for rhein detection. The mass transition followed was m/z 283.06→239.0. The calibration curve was linear in the concentration range of 10-8000 ng/mL for the biofluids. The intra- and interday precisions were less than 10%. The relative standard deviation of recovery was less than 15% in biological matrices. The pharmacokinetic data showed that rhein was rapidly transported into biofluids, and exhibited a peak concentration 1 h after rhubarb administration. The elimination rate of rhein was slow. The AUCcerebrospinal fluid /AUCplasma (AUC is area under curve) of rhein was approximately 17%, indicating that portions of rhein could pass the impaired blood-brain barrier. The method was successfully applied to quantify rhein in the biofluids of all patients. The data presented can help to guide clinical applications of rhubarb for treating traumatic brain injury.