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Objective:To investigate the effects of polyethylene glycol 400 （PEG400） on the pharmacokinetics and anti-inflammatory effect of baicalin， and to preliminarily explore the anti-inflammatory effects of baicalin and its main metabolite baicalein 6-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucuronide （B6G） by molecular docking. Method:Rats were randomly divided into two groups with water and PEG400 as the dissolving matrix， and rats were administrated the equal dose of baicalin aqueous solution （baicalin+water group） and baicalin PEG400 solution （baicalin+PEG400 group）. After the plasma samples were processed at different time periods， the concentrations of baicalin and B6G in rat plasma were determined by ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and pharmacokinetic parameters were processed by DAS 3.2.2 software. Mice were randomly divided into a blank group （normal saline， 20 mL·kg<sup>-1</sup>）， aspirin group （dose of 0.2 g·kg<sup>-1</sup>）， baicalin/baicalin+PEG400 high and low dose （3.0， 1.5 g·kg<sup>-1</sup>） groups， after continuous administration for 7 days， the mouse ear swelling and foot swelling models were established， and the swelling degree and swelling inhibition rate were calculated. Result:The pharmacokinetic study showed that compared with baicalin+water group， the plasma concentrations of baicalin and B6G increased after administration of baicalin PEG400 solution， and the area under the curve （AUC<sub>0-</sub><italic><sub>t</sub></italic>） increased by 2.36， 1.97 times， and the peak concentration （<italic>C</italic><sub>max</sub>） increased by 2.12， 1.65 times， respectively. The results of mouse ear and foot swelling inflammation models showed that the anti-inflammatory effect was enhanced after intragastric administration of baicalin PEG400 solution. In addition， molecular docking results showed that baicalin and B6G could site bind to multiple target proteins ［tumor necrosis factor （TNF）-<italic>α</italic>， interleukin （IL）-6， IL-1<italic>β</italic>， prostaglandin E<sub>2</sub> （PGE<sub>2</sub>） and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）］ with higher affinity， which was superior to the positive drug aspirin. Conclusion:PEG400 can increase the plasma concentration of baicalin and its main metabolite B6G， and enhance the anti-inflammatory effect. Baicalin and B6G can form strong hydrogen bonds with various inflammatory factors and of nuclear transcription factors， it is speculated that baicalin and B6G jointly play an anti-inflammatory role.
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The aim of this study was to investigate the effects of polyethylene glycol (PEGs) with different molecular weights (MW: 400, 1 000, 4 000) on the pharmacokinetics of baicalin, and preliminarily analyze its mechanism. Rats were gavaged with baicalin (168 mg·kg-1) + aqueous solution or baicalin + PEGs solution and plasma samples were collected from 0 to 24 h after administration. The concentration of baicalin and its main metabolite baicalein 6-O-β-D-glucuronide (B6G) were determined at different time points by UPLC-MS/MS, and the pharmacokinetic parameters were calculated with DAS 3.0 software. The results showed that PEGs with different molecular weights could effectively increase the AUC0-t of baicalin and B6G, increase the Cmax, and prolong the t1/2, effectively increasing the concentration of baicalin and B6G in vivo. The mechanism may be by promoting the activity of uridine diphosphate glucuronosyl-transferases 1A8 (UGT1A8) and 1A9 (UGT1A9), thereby increasing the transformation rate of baicalin and B6G. The rate of metabolism of B6G was faster than that of baicalin, suggesting that PEGs had a higher affinity for UGT1A8, and PEG400 had the most significant effect. The purpose of this study was to provide a basis for the clinical safe use of baicalin and other flavonoids and the design of new dosage forms with the participation of PEGs. The animal experiment protocol in this study was approved by the Experimental Animal Ethics Committee of Guizhou Medical University.
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Objective::To investigate the effect of polyethylene glycol 400 (PEG400) on rat bile excretion of baicalin and its main metabolite [baicalein 6-O-β-D-glucuronide (B6G)], and to analyze its mechanism of action. Method::Rats were randomly divided into baicalin+ water group and baicalin+ PEG400 group, the anesthesia was induced by intraperitoneal injection of 10% chloral hydrate (dose of 4 mL·kg-1) to prepare a rat bile duct intubation model. After the rats were fully awake, rats were given baicalin aqueous solution and baicalin PEG400 solution with dose of 168 mg·kg-1 for baicalin, respectively. And bile was collected from 0 h to 12 h after administration. UPLC-MS/MS was used to determine the concentration of drug excreted through bile at different time periods. Thermo Hypersil GOLD C18 column was used with acetonitrile (A)-0.1% formic acid solution (B) as the mobile phase for gradient elution (0-9 min, 90%-27%B; 9-10 min, 27%-90%B; 10-12 min, 90%B), the flow rate was 0.3 mL·min-1, the column temperature was 30 ℃, the injection volume was 5 μL. The mass spectra were obtained in positive ion mode with electrospray ionization (ESI). The effects of PEG400 on the activities and expressions in rat liver of uridine diphosphate glucuronyltransferase (UGT) 1A8 and UGT1A9 were studied in vitro incubation assay and enzyme linked immunosorbent assay (ELISA). Result::Compared with the baicalin+ water group, in the baicalin+ PEG400 group, the bile cumulative excretions of baicalin and B6G increased by 1.8 times and 2.1 times within 12 h, respectively. PEG400 increased the enzyme activities of UGT1A8 and UGT1A9 by 2.0 times and 1.5 times, and their concentrations in liver were increased by 2.2 times and 1.3 times, respectively. Conclusion::PEG400 can significantly increase the bile excretion of baicalin and its main metabolite B6G by enhancing the activities and expressions of UGT1A8 and UGT1A9, and its promoting effect on bile excretion of B6G is greater than that of baicalin, which provides a basis for the rational clinical application of PEG400 and the design of new dosage forms of flavonoids such as baicalin.
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The study aimed to establish an UPLC-MS/MS method for the determination of baicalin in rat plasma,in order to study the effect of PEG400 on pharmacokinetics of baicalin and baicalein in normal and gut microbiotadysbiosis rats. Plasma was precipitated with ethyl acetate and determined by UPLC-MS/MS method,with genistein as an internal standard. In terms of specificity,linearity,range,accuracy,precision and stability,the method was suitable for the determination of baicalin in plasma. The gut microbiotadysbiosis rat model was induced through the oral administration with lincomycin hydrochloride(5 g·kg-1·d-1) for one week. Samples of plasma of rats were obtained at different time points,after the rats were administrated with baicalin,baicalin and PEG400. Baicalin in rats were detected by UPLC-MS/MS method,and pharmacokinetic parameters were calculated by DAS 3. 2. 2 software. The results showed that the β-glucosidase activity and the number of colonies in the feces of gut microbiotadysbiosis rats induced by lincomycin hydrochloride were significantly reduced. The Cmaxand AUC0-tof the baicalinand PEG400 group in the intestinal flora were significantly lower than those in the normal rat baicalin and PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the baicalin group and the baicalin+PEG400 group of gut microbiotadysbiosis rats. The Cmaxand AUC0-tof the normal rats baicalin group were significantly higher than those of the gut microbiotadysbiosis rats baicalin group and the baicalin + PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the normal rat baicalein and PEG400 group and the baicalein group. The Cmaxand AUC0-tof the baicalein group in the gut microbiotadysbiosis rats were lower than those in the normal baicalein group,but significantly higher than those in the baicalein and PEG400 group. PEG400 could increase the absorption of baicalin in normal rats,but is ineffective in gut microbiotadysbiosis rats,with no impact on the absorption of baicalein in rats.
Subject(s)
Animals , Rats , Chromatography, Liquid , Dysbiosis , Drug Therapy , Flavanones , Pharmacokinetics , Flavonoids , Pharmacokinetics , Gastrointestinal Microbiome , Polyethylene Glycols , Tandem Mass SpectrometryABSTRACT
AIM To investigate the protective effects of Miaoling Natto Capsules (MNC) on myocardial ischemia-reperfusion injury (MIR) in rats.METHODS Forty-eight healthy male Sprague-Dawley (SD) rats randomly divided into sham group,model group,positive control group (propranolol),MNC groups (low dose,medium dose,and high dose groups) underwent corresponding 7-day oral administration at a frequency of twice daily (rats of the sham group and the model group were dosed with saline water at 1 mL/100 g).Anesthetized by 8％ chloral hydrate,rat models were made by left anterior descending coronary artery ligation,30 min coronary occlusion followed by 3 h of reperfusion for ST segments and T waves monitoring,and rats in the sham group were performed opening and suture procedures.The rats had their serum levels of acetic transaminase (AST),lactate dehydrogenase (LDH),creatine kinase isoenzyme (CK-MB),cardiac troponin-Ⅰ (cTn-Ⅰ),superoxide dismutase (SOD),malondialdehyde (MDA),and tumor necrosis factor-α (TNF-α) detected,real time ECG changes monitored and myocardial infarction area assessed by TTC.RESULTS Compared with the sham group,the model group was observed with markedly elevated ST segments or high T waves rise,significantly increased activities of CK-MB,LDH,AST and the content of cTnⅠ,MDA,TNF-α,and decreased activity of SOD (P ＜ 0.01 or P ＜ 0.001).Compared with the model group,the positive control group and the low,medium and high dose MNC groups achieved controlled ST segments elevation or greater T waves amplitude,significantly decreased activities of CKMB,LDH,AST and the content of cTnⅠ,MDA,TNF-α increased activity of SOD (P ＜0.01 or P ＜0.05) and mycocardial infact range reduction (P ＜ 0.001).CONCLUSION MNC is protective to rats with myocardial ischemia-reperfusion injury.
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OBJECTIVE@#To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells (BMSCs) with ultrasound-exposed microbubbles (UM) pretreatment.@*METHODS@#Third generation BMSCs were divided into four groups control group, ultrasound (US) group, UM group and ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were performed to determine the levels of CXCR4 mRNA transcription and protein expression, respectively. Third generation BMSCs were labeled with Fluo-α/AM and divided into three groups: control group, US group and UM group, and fluorescence intensities in the cells were observed immediately, 5 min and 15 min after intervention under fluorescence microscope. The calcium iron levels in the cells were analyzed. BMSCs were divided into five group: group A without calcium in the medium, group B, group C, group D and group E containing calcium chloride with concentration of l mol, 2 mol, 4 mol, anti-calcium-sensing receptor antibody, respectively. RT-PCR and western blot were performed to determine the levels of CXCR4 mRNA transcription and proteins expression of the third generation BMSCs of each group, respectively.@*RESULTS@#The levels of CXCR4 mRNA transcription and protein expression between US group and control group had no statistically significant difference (P > 0.05) shown by RT-PCR and western blot; the transcription level in the UM group was significantly higher than that in US group and control group (P 0.05), which in the cells of UM group was significantly higher than that in the cells of both US group and control group (P < 0.05). Compared to group A, expressions of CXCR4 of group B to D were significantly increased in concentration-dependent manner showed by RT-PCR and western blot (P < 0.05). Compared to group C, expressions of CXCR4 of group E were significantly decreased (P < 0.05).@*CONCLUSIONS@#UM can promote the influx of calcium in BMSCs and increase mRNA transcription and protein expression of CXCR4. The latter may partly be caused by influx of calcium.
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Objective: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells (BMSCs) with ultrasound-exposed microbubbles (UM) pretreatment. Methods: Third generation BMSCs were divided into four groups control group, ultrasound (US) group, UM group and ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were performed to determine the levels of CXCR4 mRNA transcription and protein expression, respectively. Third generation BMSCs were labeled with Fluo-α/AM and divided into three groups: control group, US group and UM group, and fluorescence intensities in the cells were observed immediately, 5 min and 15 min after intervention under fluorescence microscope. The calcium iron levels in the cells were analyzed. BMSCs were divided into five group: group A without calcium in the medium, group B, group C, group D and group E containing calcium chloride with concentration of l mol, 2 mol, 4 mol, anti-calcium-sensing receptor antibody, respectively. RT-PCR and western blot were performed to determine the levels of CXCR4 mRNA transcription and proteins expression of the third generation BMSCs of each group, respectively. Results: The levels of CXCR4 mRNA transcription and protein expression between US group and control group had no statistically significant difference (P > 0.05) shown by RT-PCR and western blot; the transcription level in the UM group was significantly higher than that in US group and control group (P 0.05), which in the cells of UM group was significantly higher than that in the cells of both US group and control group (P < 0.05). Compared to group A, expressions of CXCR4 of group B to D were significantly increased in concentration-dependent manner showed by RT-PCR and western blot (P < 0.05). Compared to group C, expressions of CXCR4 of group E were significantly decreased (P < 0.05). Conclusions: UM can promote the influx of calcium in BMSCs and increase mRNA transcription and protein expression of CXCR4. The latter may partly be caused by influx of calcium.
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<p><b>OBJECTIVE</b>To study the fingerprint of dragon's blood resina draconis by high performance liquid chromatography.</p><p><b>METHOD</b>The samples are extracted with methanol and separated on a Eclipse XDB-C18 column (4.6 mm x 150 mm, 5 microm) with the mobile phase of acetonitrile-H2O in gradient mode, and the flow rate was 1.0 mL x min(-1), the detection wavelength was 275 nm and the temperature of column was 40 degrees C. Loureirin B was used as the reference compound.</p><p><b>RESULT</b>HPLC fingerprint of dragon's blood was established and the similarity of the fingerprint was compared.</p><p><b>CONCLUSION</b>The method is simple, accurate, and can be used to control the quality of dragon's blood.</p>
Subject(s)
Chromatography, High Pressure Liquid , Methods , Dracaena , Chemistry , Plant Extracts , Reference Standards , Plants, Medicinal , Chemistry , Quality Control , Reproducibility of Results , Resins, Plant , Reference StandardsABSTRACT
Objective To explore the clinical manifestations of ultrasonography(US),99mTc-methoxyisobutylisonitrile(99mTc-MIBI),and 131I whole body scan(131I-WBS)of patients with differentiated thyroid carcinoma(DTC)and cervical lymph node metastasis.Methods A total of 117 cases received examinations of US and 99mTc-MIBI before uses of 131I and received 131I-WBS after 6 d of 131I treatment.Combined with serum thyroglobulin(Tg),131I-SPECT/CT,lymph node biopsy and clinical follow-up of patients,cervical lymph node metastases were identified.Results In 117 patients,the sensitivity of US,99mTc-MIBI and 131I-WBS were 76.5%,67.1% and 83.5%(P
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ObjectiveTo explore the clinical and epidemiological value of semi-quantitative regional cerebral blood flow(rCBF)imaging in children with school phobia. Methods A total of 20 cases diagnosed with school phobia were examined with rCBF.Twelve were males and the other 8 were females.The mean age was(14.2?2.1)years(11-18 years).Semi-quantitative analysis methods were used to investigate the correlations among gender,age and rCBF. ResultsThere were significant differences in the rCBF of right fronto-parietal lobe,right occipital lobe,caput and putamen,left thalamus and hippocampus,and temporo-occipital lobe between males and females(P0.05).Only the PI of left temporo-parietal lobe of those ≥ 15 years old was significantly different from that of those