1.Metabolites and metabolic pathways of mesaconitine in rat liver microsomal investigated by using UPLC-MS/MS method in vitro.
Yun-Feng BI ; Shu LIU ; Rui-Xing ZHANG ; Feng-Rui SONG ; Zhi-Qiang LIU
Acta Pharmaceutica Sinica 2013;48(12):1823-1828
Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of mesaconitine in rat liver microsomes were identified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4) containing 0.5 gL-1 microsomal protein and 50 micro molL-1 mesaconitine was prepared. The above reaction mixture was divided into six groups, and the volume of each group was 200 micro L. The incubation mixture was pre-incubated at 37 degrees C for 2 min and the reactions were initiated by adding NADPH generating system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was added to each group to stop the reaction. The metabolites of mesaconitine were investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were found in the incubation system. The structures were characterized according to the data from MS/MS spectra and literatures. The metabolic reactions of mesaconitine in rat liver microsomes included the demethylation, deacetylation, dehydrogenation and hydroxylation. The major metabolic pathways of mesaconitine in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP) isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D), diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C), separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were also more important CYP isoforms for the metabolism reactions of mesaconitine, but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver microsomes.
Aconitine
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analogs & derivatives
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metabolism
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Animals
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Chromatography, High Pressure Liquid
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Cytochrome P-450 CYP3A
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metabolism
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Cytochrome P-450 CYP3A Inhibitors
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System
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metabolism
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Enzyme Inhibitors
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pharmacology
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Ketoconazole
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pharmacology
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Male
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Metabolic Networks and Pathways
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Microsomes, Liver
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enzymology
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metabolism
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Quinine
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pharmacology
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Rats
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Rats, Sprague-Dawley
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Sulfaphenazole
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pharmacology
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Tandem Mass Spectrometry
2.Efftects of Tianma Xingnao Capsule on Brain Blood Circulation in Mice and Rats
Rui LIU ; Yu YUN ; Jindan ZHEN ; Jiashuo ZHANG ; Zhiqiang SHEN
Journal of Kunming Medical University 2006;0(06):-
Objective To study the protective effects of Tianma xingnao capsule on brain blood circulation in mice and rats.Methods The arteria carotis externa was ligated,and arteria carotis interna was kept.The left carotid artery was exposed and placed over an ultrasonic flow probe.The brain flow volume was recorded with an Ultrasonic Volume.The pursiness time of mice was observed to evaluate the effect of Tianma xingnao capsule on cerebral ischemia and anoxia.The permeability of normal blood-cerebral barrier was investigated in mice.Results Tianma xingnao capsule significantly increased brain blood flow and prolonged mouse pursiness time.Tianma xingnao capsule at a dose of 4 g/kg significantly elevated the content of Evans in mouse brain.Conclusions Tianma xingnao capsule can increase the brain blood flow in rats and improve brain blood circulation in mice.It is obviously advantageous to protect against cerebral ischemia and hypoxia.
3.Mediator effect of coping style in relationship between hope level and subjective well-being of empty-nesters in urban community
Lina WANG ; Yun RUI ; Yuqiu ZHOU ; Xiujuan LIU ; Hong SU
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(7):644-646
Objective To explore the mediator effect of coping styles in relationship between hope level and subjective well-being of empty-nesters in urban community.Methods 208 empty-nesters were tested with Herth Hope Scale,Coping Style Questionnaire and Subjective Well-Being to investigate the influence and the pathways of hope and coping styles on subjective well-being with structural equation modeling.Results Influence of hope level on subjective well-being of empty-nesters in urban community accorded with completely-mediated model (x2/df =1.971,GFI =0.955,AGFI =0.911,RMSEA =0.068),and influence of hope level mediated by positive coping styles accounted for 41.76%(Z=3.692,P<0.01).Conclusion The influence of hope level on subjective well-being is mediated mainly by positive coping styles for empty-nesters in urban community.
4.Effects of Naoxintong Drip Pill in Activating Blood and Removing Blood-stasis and on Myocardial and Cerebral Ischemia
Yuanjing LI ; Yanmin WU ; Jing RUI ; Yun LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2000;0(05):-
Objective To investigate effects of Naoxintong drip pill (NDP) in activating blood and removing blood-stasis and on myocardial and cerebral ischemia. Methods The in-vivo effect of NDP on thrombosis, aggregation of platelets, blood viscosity, microcirculation, acute myocardial and cerebral ischmia and the focal cerebral-infarction were observed for study the pharmacodyamic effect of NDP. Results NDP could significantly inhibit the formation of thrombosis and maximal aggregation rate of platelets, and decrease viscosity in whole blood and plasma in rats with blood stasis. It could also promote auricular microcirculation, prolong the survival time of mice with cerebral ischemia, improve the electrocardiogram of ischemic rats, reduce the focal cerebral-infarction area and improve behavior disorder. Conclusion NDP possesses actions of activating blood and removing blood-stasis and improving myocardial and cerebral ischemia and focal cerebral-infarction.
5.Study on Arbuscular Mycorrhizae of Panax notoginseng
Jia-Hong REN ; Rui-Xiang LIU ; Yun-Ling LI ;
Microbiology 1992;0(02):-
Arbuscular mycorrhizal fungi can infect the roots of Cercidiphyllaceae and form arbuscular mycorrhizae.Infection rate is from 12% to 30%,but infection strength is weak.4 species of Acaulospora and 11 species of Glomus were isolated and identified,including Acaulospora tuberculata,A.spinosa,A.foveata,A.denticulate,Glomus geosporum,G.clarum,G.constrictum,G.monosporum,G.laroideum,G.versifome,G.microcarpum,G.mosseae,G.hoi,G.halonatum and G.reticulatum.Among them,G.cercidiphyllorum is advantage species.So AMF may be a potent resource of biology which can stimulate the growth of Panax notoginseng.
6.The role of galactomannan detection in the diagnosis of invasive pulmonary aspergillosis in critically ill patients
Yan SHI ; Dawei LIU ; Yun LONG ; Ye LIU ; Xi RUI ; Xiang ZHOU ; Xiaoting WANG ; Wei DU
Chinese Journal of Internal Medicine 2009;48(3):225-230
Objective To evaluate the usefulness of serum galactemannan(GM) for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients. Methods Study was conducted between February 2007 and July 2008. Included patients on admission ICU who suffer from suspected IPA. GM test and culture were collected 2 weekly. Chnical feature, mycological evidence and optical density index (ODI) were noted. Clinically invasive fungal infection(IFI) were defined proven, probable and possible. The patients were classified into neutropenia, non-neutropenia and treated with immunosuppressive agents, non-neutropenia and non-immunosuppressive agents. To compared of the sensitivity and specificity of GM in different patients. Results 94 patients were included, 4 patients were proven, 29 patients were probable, 34 patients were possible IFI, 27 patients were non-IPA. The positive rate of the GM was 31.9% (30/94). The sensitivity and specificity of GM in proven cases and probable cases are 66.7% and 92.6%. GM assay tended to become positive earlier than the culture 2-10(5.33±2.17)d. We found that differences in patient diagnosis and selection might account for the disparities seen for positive rate for the GM test. There was positive in three of the four patients with proven, the positive rate of GM was 65.5% for probable cases, for possible cases was 17.6%, for non-IPA cases was 7.4% (P=0.001). For patient with neutropenia , treated with immunosuppressive agents and without immunosuppressive agents, the positive rate of GM was 52.9%vs 41.7% vs 34. 6% (P=0.015) ;the sensitivity was 80.0% vs 70. 0% vs 53.8% (P=0.011), the ODI was 1.365 (0.582-6.736) vs 1. 123 (0. 623-6.868) vs 0.554 (0.522-0.823), P=0. 005, respectively. Conclusion These results show that GM test is useful for early diagnosis IPA in critically ill patients. Differences in patient selection and diagnosis might account for the disparities seen for positive rate and sensitivity for the GM test. It has been higher sensitivity and ODI in the patient treated by immunosuppressive agents.
7.Relation between Chinese Medical Constitutions and Chemotherapy-induced Leucopenia in Breast Cancer Patients: a Clinical Study.
Yi LIU ; Qing-hua CHEN ; Ye SUN ; Yun CAI ; Rui WANG ; Ping-ping HAN ; Zhe ZHANG ; Rui WANG ; Feng YE
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(6):664-667
OBJECTIVETo analyze the relationship between Chinese medical constitutions and chemotherapy-induced leucopenia (CIL) of primary breast cancer patients.
METHODSTotally 306 breast cancer patients undergoing adjunctive chemotherapy for the 1st time, and effective 291 breast cancer patients were recruited in this study.Nine Basic Constitutional Scale was used before first chemotherapy. Chinese medical constitutions were classified and quantitatively scored. The highest grading for any item of adverse reactions in each case during the whole chemotherapy course was recorded after chemotherapy. Data were statistically analyzed using SPSS16.0.
RESULTSThere was no significant difference in CIL between different chemotherapy regimens and various Chinese medical constitutions of breast cancer patients (P > 0.05). Yang deficiency constitution is one risk factor for CIL. The higher the score of yang deficiency constitution, the more severe the CIL.
CONCLUSIONSYang deficiency constitution was correlated with the degree of CIL. The higher the score of yang deficiency constitution, the greater the risk of III-IV grade CIL in breast cancer patients.
Breast Neoplasms ; complications ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukopenia ; chemically induced ; Medicine, Chinese Traditional ; Yang Deficiency
8.Silk fibroin scaffolds seeded with stem cells for repair of tunica albuginea defect in rabbits
Ya ZHANG ; Yun ZHOU ; Xuegang LIAN ; Xiaofen MIAO ; Rui WANG ; Lin LIU
Chinese Journal of Trauma 2014;30(6):611-615
Objective To investigate the effect of silk fibroin scaffolds seeded with adipose mesenchymal stem cells (ADMSCs) in remodeling fiber for tunica albuginea defect in rabbits.Methods Fifty-six New Zealand rabbits were divided into 4 groups according to the random number table after a defect was created in the tunica albuginea:Group A (the defect was repaired with silk fibroin),Group B (with silk fibroin seeded with ADMSCs),Group C (with autologous tunica vaginalis) and Group D (left unrepaired),with 14 rabbits per group.Tunica albuginea sections were obtained for HE staining,Sirius red staining,Hart staining and immunofluorescence staining of macrophages at 6 and 12 weeks after surgery.Results At 12 weeks after surgery,HE staining revealed chaotically distributed new fiber ingrowth in Group D and orderly ingrowth in Groups A,B,and C.At 12 weeks after surgery,Sirius red staining revealed mean area of type Ⅰ collagen fibers was greater than that of type Ⅲ in Groups A (98 780 ±4 190 vs 51 177 ±5 464),B(94 855 ±9 010 vs 50 815 ±3 895),and C(99 860 ±6 015 vs 50 948 ± 6 595),but the difference in area of collagen fiber of the same type was insignificant among the three Groups.Moreover,less type Ⅰ collagen fibers (79 386 ±2 237) and more type Ⅲ collagen fibers (85 278 ± 2 645) were observed in Group D compared with other three Groups (P < 0.01).At 12 weeks after surgery,Hart staining showed the mean area of elastic fibers in Groups A,B,C,and D was 2 805 ± 90,2 849 ±84,3 068 ±485,and 1 961 ±96 respectively.There was no statistical difference between Groups B and C,but less amount of fibers was observed in Group A (P < 0.01) and least amount was observed in Group D (P <0.01).At 6 weeks after surgery,the number of infiltrating macrophages in Groups A,B,C and D was 4.10 ± 0.87,3.80 ± 0.78,3.70 ± 0.94,and 6.80 ± 1.63 respectively.There was no statistical difference in the number of macrophage infiltration among Groups A,B and C,but all were lower than that in Group D (P < 0.01).Conclusion Silk fibroin seeded with ADMSCs is comparable to autologous grafts for repair of tunica albuginea defect in rabbits.
9.Analysis of clinical effects of percutaneous vertebroplasty and percutaneous kyphoplasty in treating osteoporotic vertebral compression fracture.
Yao WU ; Feng WANG ; Jian-Qiang ZHOU ; Cai-Yun LIU ; Rui-Xing WU
China Journal of Orthopaedics and Traumatology 2014;27(5):385-389
OBJECTIVETo explore the clinical outcomes of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral compression fracture (OVCF).
METHODSFrom January 2007 to February 2010, the data of 40 patients with osteoporotic vertebral compression fracture underwent treatment were retrospectively analyzed. Of them,20 patients were treated with PVP (PVP group), there were 8 males and 12 females with an average age of (66.37 +/- 2.34) years old (54 to 81); 20 patients were treated with PKP (PKP group), there were 11 males and 9 females with an average of (65.12 +/- 3.21) years old (56 to 79). Postoperative at 1 week, 12 weeks, 1 year, pain and daily life function were respectively assessed by visual analogue scale (VAS) and Barthel index (BI); and anterior height of responsibility vertebra, Cobb angle were measured by X-rays.
RESULTSIn PVP group, 1 case complicated with bone cement leakage without clinical symptoms and no operation to treat. No postoperative infection and deep vein thrombosis were found between two groups. All patients were followed up more than 1 year, pain and daily life function has obviously improved than preoperative (P < 0.01); and there was no significant difference on 1 week, 12 weeks, 1 year after operation (P > 0.05); there was no significant difference between two groups (P > 0.05). In PVP group, there was no significant difference in anterior height of responsibility vertebra, Cobb angle before and after operation;and in PKP group, postoperative data has obviously improved than preoperative (P < 0.01), but there was no significant difference postoperative at 1 week, 12 weeks, 1 year (P > 0.05); there was no significant difference between two groups at 1 week, 12 weeks, 1 year after operation.
CONCLUSIONBoth the methods can obviously relieve pain and completely or partly recover daily life function in treating OVCF. But PKP has advantages of recovery of anterior height of responsibility vertebra and correction of Cobb angle, especially for serious compression.
Aged ; Aged, 80 and over ; Female ; Fractures, Compression ; diagnostic imaging ; physiopathology ; surgery ; Humans ; Kyphoplasty ; Male ; Middle Aged ; Osteoporotic Fractures ; diagnostic imaging ; physiopathology ; surgery ; Radiography ; Recovery of Function ; Retrospective Studies ; Spinal Fractures ; diagnostic imaging ; physiopathology ; surgery ; Spine ; surgery ; Treatment Outcome
10.The metabolic fingerprint of the compatibility of Radix Aconite and Radix Paeoniae Alba and its effect on CYP450 enzymes.
Yun-Feng BI ; Zhong ZHENG ; Zi-Feng PI ; Zhi-Qiang LIU ; Feng-Rui SONG
Acta Pharmaceutica Sinica 2014;49(12):1705-1710
Using a UPLC-MS/MS (MRM) and cocktail probe substrates method, the metabolic fingerprint of the compatibility of Radix Aconite (RA) and Radix Paeoniae Alba (RPA) and its effect on CYP450 enzymes were investigated. These main CYP isoforms include CYP 1A2, CYP 2C, CYP 2E1, CYP 2D and CYP 3A. Compared with the inhibition effect of RA decoctions on CYP450 isoforms, their co-decoctions of RA and RPA with different proportions can decrease RA' inhibition on CYP3A, CYP2D, CYP2C and CYP1A2, but can not reduce RA' effect on CYP2E1. The metabolic fingerprints of RA decoction and co-decoctions with different proportions of RPA in CYP450 of rat liver were analyzed by UPLC-MS. Compared with the metabolic fingerprints of RA decoction, the intensity of diester-diterpenoid aconitum alkaloids decreased significantly, while the intensity of monoester-diterpenoid alkaloids significantly increased in the metabolic fingerprints of co-decoctions of RA and RPA. The results suggest that RA coadministration with RPA increased the degradation of toxic alkaloid and show the effect of toxicity reducing and efficacy enhancing.
Aconitum
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chemistry
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Alkaloids
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chemistry
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Animals
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Chromatography, High Pressure Liquid
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Cytochrome P-450 Enzyme Inhibitors
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chemistry
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Drugs, Chinese Herbal
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chemistry
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Liver
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drug effects
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enzymology
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Metabolome
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Paeonia
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chemistry
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Rats
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Tandem Mass Spectrometry