Determination of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dogs by using UHPLC MS/MS Application in a pharmacokinetic study.

Oroxylin A, obtained from the root of Scutellaria baicalensis Georgi, is a flavonoid with antitumor and other pharmacological activities. Our previous studies showed for the first time that it is mainly metabolized to oroxylin A sodium sulfonate by sulfotransferase enzymes in beagle dogs. In this study, rapid, universal, selective, and robust ultra-high-performance liquid chromatography-tandem mass spectrometry methods were established and fully validated to quantitatively detect oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dog plasma. The quantitative analysis for oroxylin A sodium sulfonate was reported for the first time. Plasma samples were processed with acetonitrile, a universal protein precipitant. Gradient elution was performed to resolve carryover effects and to achieve separation efficiency and sufficient chromatographic retention. The linear relationships of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in plasma were in the range of 2.0-500.0, 5.0-500.0, and 1.881-940.5 ng/mL, respectively. The assay method was successfully applied to pharmacokinetic study. This is the first paper that reveals the pharmacokinetic profile of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate after single-dose intravenous and oral administration of Oroxylin A in beagle dogs.

Oroxylin A, a methylated metabolite of baicalein, exhibits a stronger inhibitory effect than baicalein on the CYP1B1-mediated carcinogenic estradiol metabolite formation.

Human cytochrome P450 1B1 (CYP1B1)-mediated formation of 4-hydroxyestradiol (4-OHE2) from 17ß-estradiol plays an important role in the progression of human breast cancer, while the biotransformation of 17ß-estradiol to 2-hydroxyestradiol mediated by cytochrome P450 1A1 (CYP1A1) is considered as a less harmful pathway. In this study, inhibitory effects of flavonoids baicalein and oroxylin A, a metabolite of baicalein in human body, on CYP1A1 and 1B1 activities were investigated in vitro. The inhibition intensities of baicalein and oroxylin A towards CYP1B1 were greater than towards CYP1A1 with a mixed mechanism. In addition, oroxylin A showed a stronger inhibitory effect than baicalein towards the CYP1B1-mediated 17ß-estradiol 4-hydroxylation, with the IC50 values of 0.0146 and 2.27 µM, respectively. Docking studies elucidated that oroxylin A had a stronger binding affinity than baicalein for CYP1B1. In MCF-7 cells, compared with baicalein-treated groups, oroxylin A with lower doses decreased and increased the formation of 4-OHE2 and 2-hydroxyestradiol, respectively, with a preferential induction of mRNA of CYP1A1 over CYP1B1. In conclusion, this study demonstrated that oroxylin A showed a stronger inhibitory effect than baicalein on CYP1B1-mediated 4-OHE2 formation in MCF-7 cells, providing crucial implications for their possibly preventive/therapeutic potential against breast cancer via inhibition of CYP1B1, particularly of oroxylin A.

Comparative Analysis of the Wounded in Patients and Deaths in a Hospital Following the Three Major Earthquakes in Western China.

The purpose of this study was to analyze the injury characteristics of patients and therapeutic strategies for patients injured in the last three big earthquakes in China, so as to provide a reference for the improvement of emergency plans for earthquakes. The analysis was based on the data provided by the Mianyang Central Hospital (MCH) from May 12th, 2008 to September 26th, 2017. Microsoft EXCEL software was used for data input, and SPSS was used for statistical analysis. A total of 1,390 earthquake-related patients were hospitalized in MCH. Most patients were admitted to the hospital within the first 2 weeks after the earthquake. The main causes for seismic injuries involved hit/strike by objects or building collapse /burying. Extremity fractures accounted for most injuries, especially 3 days after an earthquake. But soft tissue injuries cannot be neglected. Most earthquake patients were mainly treated by means of surgery and the majority were related to orthopedics. We found that different areas, population, and religions needed a tailored approach to the rescue effort. Therefore, the earthquake magnitude scale has a significant influence on mechanisms, types and severity of the injury of patients injured in earthquakes, as well as their timely transfer, management, and prognosis. Traumatic injuries are very common and thereby various surgical procedures especially orthopedic and neurosurgery are the domain of treatment modalities. Disaster preparedness and combined surgical team effort need to be focused on to reduce both mortality and morbidity.

Pharmacokinetics, tissue distribution and excretion study of Oroxylin A, Oroxylin A 7-O-glucuronide and Oroxylin A sodium sulfonate in rats after administration of Oroxylin A.

Oroxylin A (OA), as a natural flavonoid extracted from the root of Scutellaria baicalensis Georgi, is a candidate drug with multiple pharmacological activities. However, pharmacokinetic studies of OA have rarely been reported up to now. The present study aim to conduct a systemic evaluation on the pharmacokinetics, tissue distribution and excretion of OA in rats, with quantification of both OA and its two metabolites, Oroxylin A 7-O-glucuronide (OG) and Oroxylin A sodium sulfonate (OS) by the sensitive and rapid UPLC-MS/MS methods. The results show that OA was rapidly eliminated in vivo after a single-dose (2 mg/kg) i.v. administration of OA. The relative bioavailability of OA in all three i.g. administration groups (40, 120, and 360 mg/kg) were <2%. The AUC0-t values of OA, OG, and OS in rats show an apparent dose-proportionality. OA, OG, and OS all underwent a rapid and widespread tissue distribution after i.g. administration (120 mg/kg) of OA. Except for stomach and intestine, the major distribution tissues of OA and its two metabolites in rats were liver, kidney, respectively. And OA was more widely distributed in tissue than its metabolites. After i.g. administration (120 mg/kg) of OA, it was mainly excreted from the feces, and OG mainly excreted from bile and urine, while OS almost free of excretion. This work present a comprehensive pharmacokinetics information for further investigation of OA and its two metabolites.

[Impact of anxiety-depression symptoms on clinical recovery and serum TNF-alpha and IL-6 of patients with burns].

OBJECTIVE: To investigate the impact of anxiety-depression symptoms on the healing of burn wounds and the serum tumor necrosis factor a (TNF-alpha) and interleukin-6 (IL-6) in the patients with moderate and severe burns. METHODS: The patients with moderate and severe burns were divided into anxiety-depression group (24 patients) and non-anxiety-depression group (27 patients)according to the scores of anxiety-depression scores three days after burn measured by Hamilton Rating Scale for Depression (HAMD) and Hamilton Rating Scale for Anxiety (HAMA). The routine therapy was applied for both groups for 30 days. Then the scores of anxiety and depression and the degrees of wound healing were examined. The serum TNF-alpha IL-6 were measured with enzyme linked immunosorbent assay (ELISA). RESULTS: No significant decrease of the scores of depression was found before and after treatments in the anxiety-depression group (P > 0.05). The days that were needed for healing the wounds and the serum TNF-alpha and IL-6 increased in the patients with depression compared with the control group (P < 0.05). CONCLUSION: There are anxious and depressive reactions to burns by the patients. The continuous negative emotion can induce the increase of serum TNF-alpha and IL-6 and lead to delay of the healing of the burn wounds.

Determination of oroxylin A and oroxylin A 7-O-d-glucuronide in HepG2 cell lysate and subcellular fractions with SPE-UPLC-MS/MS: Cellular pharmacokinetic study to indicate anti-cancer mechanisms.

Targeting therapy of anti-cancer drugs has been gaining increasing attention. Cell pharmacokinetics have been used for in vitro disposition evaluation, as well as drug-drug interaction for anti-cancer drugs, revealing their fate after entering tumor. Flavonoid compound oroxylin A (OA) possesses strong anti-cancer effects especially on the liver and breast cancer. However, despite the low bioavailability, the disposition of OA and its active metabolite in the target cancer cells remained unclear. In current study, a highly sensitive and selective solid phase extraction (SPE)-UPLC-MS/MS method was developed and validated to simultaneously quantify the concentrations of OA and its major active metabolite oroxylin A 7-O-d-glucuronide (OG) in HepG2 cell lysate and multiple subcellular organelle fractions. The proposed method appeared to be suitable for the analysis with desirable linearity(R2 > 0.99). The relative standard deviations (RSDs) of intra- and inter-assay precision and accuracy were less than 9.9% and -7.7%, 8.4% and 11% for OA and OG in cell lysate respectively. The intra- precision and accuracy was less than 9.5% and -11.3%, 9.4% and 12.3% for OA and OG in subcellular organelles respectively. The range of absolute recovery of this method in the cell lysate was from 73.1% ±â€¯1.4% to 87.9% ±â€¯6.7%. The RSDs of matrix effects of the quality control (QC) samples were below 15%. The uptake and distribution experiments demonstrated a time-dependent transport characteristic in HepG2 cell lines. Furthermore, both OA and OG were mainly distributed into nuclei after taken up by the tumor cells. In addition, OG was also distributed into mitochondria, which indicates another potential target of OG. The present study, for the first time, reports the in vitro cell pharmacokinetics profiles of OA and OG in tumor cell lines in vitro.

[Injury characteristics and therapeutic strategy of patients injured in "8·8" Jiuzhaigou earthquake].

Objective: To summarize the injury characteristics and therapeutic strategy of patients injured in "8·8" Jiuzhaigou earthquake. Methods: The clinical data of 48 patients injured in "8·8" Jiuzhaigou earthquake who were admitted to Mianyang Central Hospital were analyzed retrospectively. There were 25 males and 23 females with an average age of 36 years (range, 5-87 years). The average interval from injury to admission was 30 hours (range, 3-53 hours). The patients from Sichuan province accounted for 45.8% (22 cases), from other province for 52.1% (25 cases), and from abroad for 2.1% (1 case). Patients were primarily hurted by collapsing houses and flying stones. Thirty-seven patients (77.1%) had single injury, mainly involving 36 patients (75.0%) in limbs, and the other 11 patients (22.9%) had multiple injuries. Ten patients (20.8%) had open fractures, including 1 case rated as typeⅠ, 2 as typeⅡ, 3 as type Ⅲa, 2 as type Ⅲb, and 2 as type Ⅲc according to Gustilo classification criteria. The abbreviated injury scale (AIS) score was 2-3 in 37 patients of single injury, and the injury severity score (ISS) was 8-22 (mean, 13.2) in 11 patients of multiple injuries. Sixteen patients (33.3%) were diagnosed as mental disorders by Hamilton rating scale for anxiety (HAMA), including 8 cases had their anxiety scores≥29, 4 cases of 21-28, 3 cases of 14-20, and 1 case of 7-13. Of the 16 patients, 2 showed suicidal tendency. Results: Except 2 referrals, 30 patients received operationï¼»28 patients (93.3%) for orthopaedic surgeriesï¼½and 16 patients received conservative treatment. The procedures included internal fixation, soft tissue debridement, external fixation, bipolar femoral head replacement, embolization of carotid cavernous sinus arteriovenous fistula, and amputation. Among the 46 patients treated in this hospital, 21 discharged from hospital at 2-12 days (mean, 6.7 days) after admission, the others received further rehabilitation in this hospital or local hospital. No undesirable consequence occurred in 16 patients with mental disorders. Five cases of infection occurred out of hospital were cured after debridement. No dead and nosocomial infection case reported. Conclusion: Intensive treatment, specialist management, multidisciplinary team, and early intervention of nosocomial infection and deep venous thrombosis are the key to improve the general level of successful earthquake medical rescue.