Objective:To investigate the therapeutic effects of matrine on CT26 tumor-bearing mice and its effect on the sterol regulatory element binding protein(SREBP)signaling pathway.Methods:A CT26 tumor-bearing mouse model w...Objective:To investigate the therapeutic effects of matrine on CT26 tumor-bearing mice and its effect on the sterol regulatory element binding protein(SREBP)signaling pathway.Methods:A CT26 tumor-bearing mouse model was established using CT26 cells.Different doses of matrine were orally administered to mice,and the tumor size and weight in each group of mice before and after administration were measured to calculate the tumor inhibition rate of matrine.Subsequently,tumor tissues were subjected to hematoxylin and eosin(HE)staining to observe morphological changes in tumor tissue,and quantitative polymerase chain reaction(qPCR)was performed to detect the expression of the genes of the lipid metabolism-related enzymes sterol regulatory element binding transcription factor 1(Srebf1),ATP citrate lyase(Acly),acetyl-Coenzyme A carboxylase alpha(Acc),and fatty acid synthase(Fasn)in tumor tissues before and after matrine intervention.Results:Compared to those in the model group,tumor-bearing mice in both the low and high-dose matrine groups showed significantly reduced tumor weights.HE staining showed that matrine significantly inhibited tumor cell proliferation in both the low and high-dose groups.The qPCR results showed that,compared with the model group,the expression levels of the genes of lipid metabolism-related enzymes Srebf1,Acly,Acc,and Fasn in tumor tissues were significantly downregulated in both the low and high-dose matrine groups.Conclusion:Matrine modulates the lipid metabolism pathway,affects tumor cell lipid metabolism,and exerts antitumor effects.展开更多
Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/o...Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/oral co-administration regime is poorly investigated. Herein,we evaluated the pharmacokinetic characteristic through a tailor-designed 3 way crossoverLatin square experiment in adult male beagle dogs. Six dogs were randomly treated by intravenous administration of lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage, named as intravenous regime. Meanwhile the other six dogs were orally administrated with lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage,named as oral regime. The pharmacokinetic feature in simultaneous oral treatment appeared to have no significant difference when compared with individual administration,even including matrine, the active metabolite of oxymatrine. In intravenous regime, the main pharmacokinetic parameters of simultaneous administration were nearly consistent with intravenous regime remedy. The collaborated application of lamivudine and oxymatrine contributed to non-distinctive pharmacokinetic fluctuations of beagle dogs in intravenous/oral regime, compared with individual employment, which established a vital base for the clinical co-administration against hepatitis B. Furthermore, the present study demonstrated that the determination of pharmacokinetics between combinational and individual therapy might assist in the development of drug compatibility in clinical therapy.展开更多
A rapid method for the simultaneous determination of berberine(BBR),matrine(MT)and oxymatrine(OMT)by nonaqueous capillary electrophoresis(NACE)was developed.Optimum separation of the analytes was obtained on a 50cm...A rapid method for the simultaneous determination of berberine(BBR),matrine(MT)and oxymatrine(OMT)by nonaqueous capillary electrophoresis(NACE)was developed.Optimum separation of the analytes was obtained on a 50cm×50μm i.d.fused-silica capillary using a non-aqueous buffer system of 70mM ammonium acetate,7.0% acetic acid and 10% acetonitrile at 25kV and 20℃.The relative standard deviations(R.S.D.)of the migration times and peak areas of the three active components were 0.06%-0.20% and 0.12%-3.41% for berberine,0.11%-0.60% and 0.74%-1.63% for matrine,0.15% and 0.45% for oxymatrine,respectively.Detection limits of berberine,matrine and oxymtrine were 0.18μg/mL,4.08μg/mL and 4.16μg/mL,respectively.In the tested concentration range,good linear relationships(0.9992 for berberine,0.9988 for matrine and 0.9988 for oxymatrine)were observed.The linear calibration ranges were 0.45-360.0μg/mL for berberine,8.16-408.0μg/mL for matrine and 20.8-416.0μg/mL for oxymatrine.This method has been successfully applied to the phytochemical analysis of alkaloids extracts from two commonly used traditional Chinese herbal drugs:Sophora flavescens Ait.(Kushen)and Cortex phellodendri chinensis(Huangbai)and their medicinal preparations.展开更多
Successive cartridge clean-up method for the simultaneous determination of matrine and oxyma- trine in biopesticides containing Sophora flavescens extract was developed and validated by UPLC. The clean-up method was e...Successive cartridge clean-up method for the simultaneous determination of matrine and oxyma- trine in biopesticides containing Sophora flavescens extract was developed and validated by UPLC. The clean-up method was established with ENVI-Carb (0.5 g) and C18 SPE (0.5 g) cartridges for the bioactive alkaloid in biopesticides from S. flavescens, and the eluate was analyzed to quantify the matrine and oxymatrine by UPLC. The developed method was validated, and the recovery and LOQ of both materials were 105.0% and 103.6%, and 0.050 and 0.684 mg·kg-1, respectively. Of the twenty one samples, the total content of matrines were analyzed by using the developed method and the result showed the developed successive clean-up method could contribute to the manufacture and control of biopesticides including matrines, and can be ap- plied to the method development for the analysis of alkaloid materials in biopesticides.展开更多
AIM: To study the antitumor effect of matrine in human hepatoma G2 (HepG2) cells and its molecular mechanism involved in antineoplastic activities. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide...AIM: To study the antitumor effect of matrine in human hepatoma G2 (HepG2) cells and its molecular mechanism involved in antineoplastic activities. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect viability of HepG2 cells. The effect of matrine on cell cycle was detected by flow cytometry. Annexin-V-FITC/PI double staining assay was used to detect cellular apoptosis. Cellular morphological changes were observed under an inverted phase contrast microscope. Transmission electron microscopy was performed to further examine ultrastructural structure of the cells treatedwith matrine. Monodansylcadaverine (MDC) staining was used to detect autophagy. Whether autophagy is blocked by 3-methyladenine (3-MA), an autophagy inhibitor, was evaluated. Expression levels of Bax and Beclin 1 in HepG2 cells were measured by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Matrine signif icantly inhibited the proliferation of HepG2 cells in a dose- and time-dependent manner, and induced G1-phase cell cycle arrest and apoptosis of HepG2 cells in a dose-dependent manner. The total apoptosis rate was 0.14% for HepG2 cells not treated with matrine. In contrast, the apoptosis rate was 28.91%, 34.36% and 38.80%, respectively, for HepG2 cells treated with matrine at the concentration of 0.5, 1.0 and 2.0 mg/mL. The remarkable morphological changes were observed under an inverted phase contrast microscope. Abundant cytoplasmic vacuoles with varying sizes were observed in HepG2 cells treated with matrine. Furthermore, vacuolization in cytoplasm progressively became larger and denser when the concentration of matrine was increased. Electron microscopy demonstrated formation of abundant autophagic vacuoles in HepG2 cells after matrine treatment. When the specif ic autophagic inhibitor, 3-MA, was applied, the number of autophagic vacuoles greatly decreased. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in HepG2 cells was greater in matrine treatment group than in control group. Fewer autophagic vacuoles were observed in the combined 3-MA and matrine treatment group when 3-MA was added before matrine treatment, indicating that both autophagy and apoptosis are activated when matrine-induced death of hepatoma G2 cells occurs. Real-time quantitative RT-PCR revealed that the expression levels of Bax gene, an apoptosis-related molecule, and Beclin 1 gene which plays a key role in autophagy were higher in matrine treatment group than in control group, indicating that Beclin 1 is involved in matrineinduced autophagy and the pro-apoptotic mechanismof matrine may be related to its upregulation of Bax expression. CONCLUSION: Matrine has potent antitumor activities in HepG2 cells and may be used as a novel effective reagent in treatment of hepatocellular carcinoma.展开更多
BACKGROUND: Hepatitis B virus (HBV) infection, a glo- bal public health problem, is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. There are more than 350 million HBV carriers in the worl...BACKGROUND: Hepatitis B virus (HBV) infection, a glo- bal public health problem, is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. There are more than 350 million HBV carriers in the world and up to one million die annually due to hepatitis B associated liv- er disease. So far no optimal treatment is available for pa- tients with chronic hepatitis B. In the paper we investigated the efficacy of intramuscular matrine in the treatment of chronic hepatitis B. METHODS: One hundred and twenty patients with chronic hepatitis B were randomly divided into matrine treatment group (n =60) and control group (n =60). The patients of the matrine group were given intramuscularly with matrine (an alkaloid extracted from a traditional Chinese herb Radix Sophorae Flavescentis by Guangzhou Ming Xing Pharmaceu cal Factory, Guangzhou, China) of 100 mg daily for 90 days in addition to conventional liver-protective drugs in- cluding glucurone, inosine, compound vitamin B and caryophyllin. The control group received conventional liv- er-protective drugs alone. Clinical manifestations and labo- ratory parameters including liver biochemistry and serum hepatitis B virus markers were monitored before and after treatment in the two groups. RESULTS: Significant differences were seen between the two groups in terms of improvement of clinical symptoms and signs, recovery of liver functions, and serum conver- sion from hepatitis Be antigen to HBe antibody and from positive to negative serum HBV DNA (P <0.05-0.01). The result of the matrine group was more marked than that of the control group. Serious side-effects were not observed except mild pain at the site of injection of matrine in a few patients. CONCLUSION: These results indicate that intramuscular matrine may be an economical, efficacious, safe drug for the treatment of chronic hepatitis B.展开更多
BACKGROUND Ulcerative colitis(UC)is a main form of inflammatory bowel disease.Due to complicated etiology and a high rate of recurrence,it is quite essential to elucidate the underlying mechanism of and search for eff...BACKGROUND Ulcerative colitis(UC)is a main form of inflammatory bowel disease.Due to complicated etiology and a high rate of recurrence,it is quite essential to elucidate the underlying mechanism of and search for effective therapeutic methods for UC.AIM To investigate the effects of astragalus polysaccharides(APS)combined with matrine on UC and associated lung injury.METHODS UC was induced in rats by colon mucosal tissue sensitization combined with trinitro-benzene-sulfonic acid-ethanol.Then,the effects of the treatments of salazopyrine,APS,matrine,and APS combined with matrine on histopathological changes of lung and colon tissues,disease activity index(DAI),colon mucosal damage index(CMDI),serum endotoxin(ET)level,serum diamine oxidase(DAO)activity,the contents of tumor necrosis factor-αand interleukin-1β,and the activities of myeloperoxidase,superoxide dismutase,and malondialdehyde in lung tissues,as well as the protein expression of zonula occludens(ZO)-1,Occludin,and trefoil factor 3(TFF3)were detected in UC rats.RESULTS The treatments of salazopyrine,APS,matrine,and APS combined with matrine reduced DAI scores and improved histopathological changes of colon and lung tissues,as well as decreased CMDI scores,ET levels,and DAO activities in UC rats.Moreover,in lung tissues,inflammatory response and oxidative stress injury were relieved after the treatments of salazopyrine,APS,matrine,and APS combined with matrine in UC rats.Furthermore,the expression of ZO-1,Occludin,and TFF3 in lung and colon tissues was increased after different treatments in UC rats.Notably,APS combined with matrine exerted a better protective effect against UC and lung injury compared with other treatments.CONCLUSION APS combined with matrine exert a synergistic protective effect against UC and lung injury,which might be associated with regulating TFF3 expression.展开更多
Objective:To study the inhibitory effect of matrine on bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway. Methods:Human T24 bladder cancer cell lines were cultured and treated with di...Objective:To study the inhibitory effect of matrine on bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway. Methods:Human T24 bladder cancer cell lines were cultured and treated with different doses of matrine(0.25 mg/mL,0.5 mg/mL and 1.0 mg/mL) as well as 20 μmol/L PI3K inhibitor LY294002 for 24 h,and the cell proliferation activity,the number of invasive cells as well as the expression of p-PI3K,p-AKT,proliferation genes and invasion genes were determined. Results:Different doses of matrine could decrease the cell viability value,the number of invasive cells as well as the expression of p-PI3K,p-AKT,MMP2 and MMP9,and increase the expression of p16,p21 and p27 in dose-dependent manner; p16,p21 and p27 expression in cells of 20 μmol/L LY29002 group were significantly higher than those of 0 μmol/L LY29002 group while MMP2 and MMP9 expression were significantly lower than those of 0 μmol/L LY29002 group(P<0.05). Conclusions:Matrine can inhibit bladder cancer cell proliferation and invasion in vitro and regulate the expression of cell cycle-inhibiting molecules and invasion-related genes through PI3K/AKT signaling pathway.展开更多
Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly d...Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly divided into A,B,C,D groups with 12 in each,group A as the normal control group and groups B.C,D as liver fibrosis models using composite modulus method with carbon tetrachloride(CCL_4).Group B was the model group,group C adopted γ— interferon lavage therapy in the second day of modeling,and group D adopted matrine lavage treatment,at 4 and8 weeks after treatment.Six rats were executed for detection of TGF- β1 and HGF,liver tissue histology and comparison fibrosis degree changes of rat liver tissue between groups.Results:Croups B,C,D showed a more significantly increased TCF- β1 at each time point compared with group A(P<0.05);Group B showed a more significantly increased TGF- β1 than groups C and D at weeks 4 and 8(P<0.05);group D showed a lowest level of TGF-β1,followed by groups C and B.HGF of group B decreased more significantly than A group at weeks 4 and 8(P<0.05);HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B(P<0.05),in which the group D showed the highest level of HGF.According to tissue histologic observation,rat liver tissue structure of group A was clear and normal,tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells;groups C and D showed a slighter liver tissue damage,cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious improvement.Conclusions:Matrine can reduce TGF- β1expression and enhance the activity of HGF,so as to realize the inhibition effect on liver fibrosis in rats.展开更多
Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and...Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.展开更多
In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully imp...In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness is not sufficient. We previously found a new effective compound for spinal cord injury, matrine, which induced axonal growth and functional recovery in acute spinal cord injury mice via direct activation of extracellular heat shock protein 90. Although our previous study clarified that matrine was an activator of extracellular heat shock protein 90, the potential of matrine for spinal cord injury in chronic phase has not been sufficiently evaluated. Thus, this study aimed to investigate whether matrine ameliorates chronic spinal cord injury in mice. Once daily intragastric administration of matrine(100 μmol/kg per day) to spinal cord injury mice were starte at 28 days after injury, and continued for 154 days. Continuous mat rine treatment improved hindlimb motor function in chronic spinal cord injury mice. In injured spinal cords of the matrine-treated mice, the density of neurofilament-H-positive axons was increased. Moreover, matrine treatment increased the density of bassoon-positive presynapses in contact with choline acetyltransferase-positive motor neurons in the lumbar spinal cord. These findings suggest that matrine promotes remodeling and reconnection of neural circuits to regulate hindlimb movement. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama(approval No. A2013 INM-1 and A2016 INM-3) on May 7, 2013 and May 17, 2016, respectively.展开更多
A series of furoxan-based nitric oxide-releasing matrine derivatives(10a-f) were synthesized.The biological evaluation showed that compounds 10a,10b,10e and 10f had stronger cytotoxic activities than 5-fluorouracil ag...A series of furoxan-based nitric oxide-releasing matrine derivatives(10a-f) were synthesized.The biological evaluation showed that compounds 10a,10b,10e and 10f had stronger cytotoxic activities than 5-fluorouracil against human hepatoma cells(HepG2) in vitro.展开更多
Matrine is a promising botanical antifungal;however, the mechanism underlying the antifungal activity is yet limited. We studied the antifungal activity of matrine and the underlying mechanism in Botryosphaeria dothid...Matrine is a promising botanical antifungal;however, the mechanism underlying the antifungal activity is yet limited. We studied the antifungal activity of matrine and the underlying mechanism in Botryosphaeria dothidea as a model strain. Matrine strongly inhibited mycelial growth of B. dothidea in a dose-dependent manner. Matrine-treated B. dothidea showed morphological and ultrastructural alterations, including shriveled hyphae, plasmolysis, and leakage of cytoplasm related to cell membrane deterioration. In addition, matrine caused significantly high conductivity and absorbance (260 nm) in extracellular matrices and low lipid contents in B. dothidea, indicating increased membrane permeability. Lipid peroxidation showed that matrine resulted in increased malondialdehyde content while enhancing the generation of reactive oxygen species and the activities of superoxide dismutase, catalase, and peroxidase. These results showed that matrine inhibited the mycelial growth of B. dothidea by enhancing cell membrane permeability via membrane lipid peroxidation.展开更多
Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、immunity liver injury of mice and chronic liver injury of rats.Methods Acute hep...Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、immunity liver injury of mice and chronic liver injury of rats.Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride(CCl4),thioacetamide(TAA),D-galactosamine(D-GalN),immunity hepatic injury model of mice induced by BCG and fat polysaccharide(LPS),chronic liver injury model of rats induced by CCl4 were introduced in the experiment.The serum ALT and AST were measured in acute hepatic injury experiments.Serum ALT,AST,AKP,ALB,TP,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen,hepatic hydroxyproline(HyP)of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride.Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4,TAA and D-GalN.The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment.Compared with the model group,the injection may obviously inhibited serum ALT,AST,TP,AKP,TRI,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4,elevated ALB、A/G,reduced the liver HyP,decreased the index of the liver and the spleen.The liver visual observation,the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue,restrain the liver cell damage,reduce the pseudolobuli formation.Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and chronic liver injury of rats induced by CCl4.展开更多
Objective The present in vivo study was undertaken to determine whether matrine,a kind of traditional Chinese medicinal alkaloid,would relax the isolated guinea pig aortic smooth muscles,if so,to investigate the mecha...Objective The present in vivo study was undertaken to determine whether matrine,a kind of traditional Chinese medicinal alkaloid,would relax the isolated guinea pig aortic smooth muscles,if so,to investigate the mechanism involved.Methods The concentration-dependent relaxation response to matrine was studied in phenylephrine or potassium chloride precontracted guinea pig aortic rings.Results Matrine(1×10-4 M-3.3×10-3 M)relaxed the endothelium denuded aortic rings precontracted submaximally with phenylephrine,in a concentration-dependent manner,and it's preincubation(3.3×10-3 M)produced a significant rightward shift in the phenylephrine dose-response curve,but had no effects on the potassium chloride-induced contraction.The anticontractile effect of matrine was not reduced by the highly selective ATP-dependent K+ channel blocker glibenclamide(10-5 M),the non-selective K+ channel blocker tetraethylammonium(10-3 M),as well as the β-antagonist propranolol(10-5 M).In either "normal" or "Ca2+-free" bathing medium,the phenylephrine-induced contraction was attenuated by matrine(3.3×10-3 M),indicating the vasorelaxation was due to inhibit of intracellular and extracellular Ca2+ mobilization.Conclusions The results obtained clearly demonstrated that matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with both the release of intracellular Ca2+ and the influx of extracellular Ca2+.展开更多
OBJECTIVE Experimental autoimmune encephalomyelitis(EAE),the classical animal model for multiple sclerosis(MS)is triggered by an impaired balance of T helper(Th)cells and regulatory T(Tregs)cells.Matrine(MAT),a quinol...OBJECTIVE Experimental autoimmune encephalomyelitis(EAE),the classical animal model for multiple sclerosis(MS)is triggered by an impaired balance of T helper(Th)cells and regulatory T(Tregs)cells.Matrine(MAT),a quinolizidine alkaloid derived from the herb Radix Sophorae Flave,has been shown to ameliorate the clinical signs,inflammatory infiltration,demyelination in acute EAE rats.However,whether MAT protect from EAE by adjusting Th and Treg cells response in specific-cellular and molecular level is unknown.METHODS Herein,MAT was tested for its effects on Th1,Th2,Th17 and Treg cells in the spinal cord of EAE mice and splenocyte-extracted from EAE mice with MOG35-55-restimulated,respectively.RESULTS Our findings revealed that MAT significantly inhibit the proliferation of splenocyte,and remarkably down-regulate the differentiation of Th1/Th17 cells with decreased expressions of CD4+IFN-γ+cells and CD4+IL-17+cells in vivo and IL-17,IFN-γ,ROR-γt,T-bet in vitro,meanwhile it dramatically up-regulate the Th2/Treg cells response associated with increased levels of CD4+TGF-β+1cells and CD4+IL-10+cells in vivo and IL-4,IL-10,TGF-β1,Foxp3 and GATA3in vitro.CONCLUSION Considering the effective therapeutic effects of MAT on EAE,it′s worth to find its new values on other autoimmune diseases.展开更多
The aim of this study was to select drugs for prevention and treatment of bovine papilloma in vitro, using bovine papilloma virus(BPV-2) infected mouse mammary epithelial(C127) cell lines as the infectious cell model ...The aim of this study was to select drugs for prevention and treatment of bovine papilloma in vitro, using bovine papilloma virus(BPV-2) infected mouse mammary epithelial(C127) cell lines as the infectious cell model system. C127 cell shapes changed with BPV infection observed under light microscopy. C127 cell shapes changed with BPV infection observed under light microscopy. PCR was used to confirm BPV infected C127 cells. mR NA levels of matrine to BPV-2 infected C127 cells were detected by RT-PCR. Apoptosis of BPV-infected C127 cells treated with matrine was analyzed by flow cytometry. Results showed that 80 μg· mL^(-1) matrine had a direct virucidal and intervention effect of BPV-2. Matrine inhibited the proliferation of BPV-infected cells. Therefore, matrine might be regarded as a therapeutic drug candidate for BPV induced bovine papilloma disease treatment in future.展开更多
Objective:To investigate the effect of matrine against biofilm formation of Escherichia coli(E.coli)in the early stage.Methods:Biofilms of E.coli(ATCC25922)was induced by using a peritoneal dialysis catheter in 96-wel...Objective:To investigate the effect of matrine against biofilm formation of Escherichia coli(E.coli)in the early stage.Methods:Biofilms of E.coli(ATCC25922)was induced by using a peritoneal dialysis catheter in 96-well plates.After treatment with matrine for 24 h,the formation of biofilm on the catheters was observed by scanning electron microscope.The expressions of the flagellar gene(fliC)and motility genes(motA and motB)were determined by qPCR,and the protein expression of fliC was detected by western blotting.Results:The biofilm formation of E.coli was suppressed by different concentrations(less than the minimal inhibitory concentration)of matrine,and the mRNA levels of motA and motB as well as the mRNA and protein expression levels of fliC were decreased in a dose-dependent manner.Conclusion:Matrine could inhibit biofilm formation of E.coli via downregulating the expression of motA,motB and fliC.展开更多
基金This work was supported by grants from the Natural Science Foundation of Fujian province(No.2020J011181).
文摘Objective:To investigate the therapeutic effects of matrine on CT26 tumor-bearing mice and its effect on the sterol regulatory element binding protein(SREBP)signaling pathway.Methods:A CT26 tumor-bearing mouse model was established using CT26 cells.Different doses of matrine were orally administered to mice,and the tumor size and weight in each group of mice before and after administration were measured to calculate the tumor inhibition rate of matrine.Subsequently,tumor tissues were subjected to hematoxylin and eosin(HE)staining to observe morphological changes in tumor tissue,and quantitative polymerase chain reaction(qPCR)was performed to detect the expression of the genes of the lipid metabolism-related enzymes sterol regulatory element binding transcription factor 1(Srebf1),ATP citrate lyase(Acly),acetyl-Coenzyme A carboxylase alpha(Acc),and fatty acid synthase(Fasn)in tumor tissues before and after matrine intervention.Results:Compared to those in the model group,tumor-bearing mice in both the low and high-dose matrine groups showed significantly reduced tumor weights.HE staining showed that matrine significantly inhibited tumor cell proliferation in both the low and high-dose groups.The qPCR results showed that,compared with the model group,the expression levels of the genes of lipid metabolism-related enzymes Srebf1,Acly,Acc,and Fasn in tumor tissues were significantly downregulated in both the low and high-dose matrine groups.Conclusion:Matrine modulates the lipid metabolism pathway,affects tumor cell lipid metabolism,and exerts antitumor effects.
基金the National Natural Science Foundation of China(Nos.30901996,81173009 and 81302722)the General Project in Education Department of Liaoning Province(No.L2013390)the Specific Science Foundation of Shenyang Pharmaceutical University(Nos.ZCJJ2014409 and ZCJJ2013402).
文摘Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/oral co-administration regime is poorly investigated. Herein,we evaluated the pharmacokinetic characteristic through a tailor-designed 3 way crossoverLatin square experiment in adult male beagle dogs. Six dogs were randomly treated by intravenous administration of lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage, named as intravenous regime. Meanwhile the other six dogs were orally administrated with lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage,named as oral regime. The pharmacokinetic feature in simultaneous oral treatment appeared to have no significant difference when compared with individual administration,even including matrine, the active metabolite of oxymatrine. In intravenous regime, the main pharmacokinetic parameters of simultaneous administration were nearly consistent with intravenous regime remedy. The collaborated application of lamivudine and oxymatrine contributed to non-distinctive pharmacokinetic fluctuations of beagle dogs in intravenous/oral regime, compared with individual employment, which established a vital base for the clinical co-administration against hepatitis B. Furthermore, the present study demonstrated that the determination of pharmacokinetics between combinational and individual therapy might assist in the development of drug compatibility in clinical therapy.
基金supported by the National Natural Science Foundation of China(No.30730110)
文摘A rapid method for the simultaneous determination of berberine(BBR),matrine(MT)and oxymatrine(OMT)by nonaqueous capillary electrophoresis(NACE)was developed.Optimum separation of the analytes was obtained on a 50cm×50μm i.d.fused-silica capillary using a non-aqueous buffer system of 70mM ammonium acetate,7.0% acetic acid and 10% acetonitrile at 25kV and 20℃.The relative standard deviations(R.S.D.)of the migration times and peak areas of the three active components were 0.06%-0.20% and 0.12%-3.41% for berberine,0.11%-0.60% and 0.74%-1.63% for matrine,0.15% and 0.45% for oxymatrine,respectively.Detection limits of berberine,matrine and oxymtrine were 0.18μg/mL,4.08μg/mL and 4.16μg/mL,respectively.In the tested concentration range,good linear relationships(0.9992 for berberine,0.9988 for matrine and 0.9988 for oxymatrine)were observed.The linear calibration ranges were 0.45-360.0μg/mL for berberine,8.16-408.0μg/mL for matrine and 20.8-416.0μg/mL for oxymatrine.This method has been successfully applied to the phytochemical analysis of alkaloids extracts from two commonly used traditional Chinese herbal drugs:Sophora flavescens Ait.(Kushen)and Cortex phellodendri chinensis(Huangbai)and their medicinal preparations.
文摘Successive cartridge clean-up method for the simultaneous determination of matrine and oxyma- trine in biopesticides containing Sophora flavescens extract was developed and validated by UPLC. The clean-up method was established with ENVI-Carb (0.5 g) and C18 SPE (0.5 g) cartridges for the bioactive alkaloid in biopesticides from S. flavescens, and the eluate was analyzed to quantify the matrine and oxymatrine by UPLC. The developed method was validated, and the recovery and LOQ of both materials were 105.0% and 103.6%, and 0.050 and 0.684 mg·kg-1, respectively. Of the twenty one samples, the total content of matrines were analyzed by using the developed method and the result showed the developed successive clean-up method could contribute to the manufacture and control of biopesticides including matrines, and can be ap- plied to the method development for the analysis of alkaloid materials in biopesticides.
基金Supported by National Natural Science Foundation of China, No. 30870364Science and Technology Support Program of Gansu Province, China, No. 0708NKCA129
文摘AIM: To study the antitumor effect of matrine in human hepatoma G2 (HepG2) cells and its molecular mechanism involved in antineoplastic activities. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect viability of HepG2 cells. The effect of matrine on cell cycle was detected by flow cytometry. Annexin-V-FITC/PI double staining assay was used to detect cellular apoptosis. Cellular morphological changes were observed under an inverted phase contrast microscope. Transmission electron microscopy was performed to further examine ultrastructural structure of the cells treatedwith matrine. Monodansylcadaverine (MDC) staining was used to detect autophagy. Whether autophagy is blocked by 3-methyladenine (3-MA), an autophagy inhibitor, was evaluated. Expression levels of Bax and Beclin 1 in HepG2 cells were measured by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Matrine signif icantly inhibited the proliferation of HepG2 cells in a dose- and time-dependent manner, and induced G1-phase cell cycle arrest and apoptosis of HepG2 cells in a dose-dependent manner. The total apoptosis rate was 0.14% for HepG2 cells not treated with matrine. In contrast, the apoptosis rate was 28.91%, 34.36% and 38.80%, respectively, for HepG2 cells treated with matrine at the concentration of 0.5, 1.0 and 2.0 mg/mL. The remarkable morphological changes were observed under an inverted phase contrast microscope. Abundant cytoplasmic vacuoles with varying sizes were observed in HepG2 cells treated with matrine. Furthermore, vacuolization in cytoplasm progressively became larger and denser when the concentration of matrine was increased. Electron microscopy demonstrated formation of abundant autophagic vacuoles in HepG2 cells after matrine treatment. When the specif ic autophagic inhibitor, 3-MA, was applied, the number of autophagic vacuoles greatly decreased. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in HepG2 cells was greater in matrine treatment group than in control group. Fewer autophagic vacuoles were observed in the combined 3-MA and matrine treatment group when 3-MA was added before matrine treatment, indicating that both autophagy and apoptosis are activated when matrine-induced death of hepatoma G2 cells occurs. Real-time quantitative RT-PCR revealed that the expression levels of Bax gene, an apoptosis-related molecule, and Beclin 1 gene which plays a key role in autophagy were higher in matrine treatment group than in control group, indicating that Beclin 1 is involved in matrineinduced autophagy and the pro-apoptotic mechanismof matrine may be related to its upregulation of Bax expression. CONCLUSION: Matrine has potent antitumor activities in HepG2 cells and may be used as a novel effective reagent in treatment of hepatocellular carcinoma.
文摘BACKGROUND: Hepatitis B virus (HBV) infection, a glo- bal public health problem, is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. There are more than 350 million HBV carriers in the world and up to one million die annually due to hepatitis B associated liv- er disease. So far no optimal treatment is available for pa- tients with chronic hepatitis B. In the paper we investigated the efficacy of intramuscular matrine in the treatment of chronic hepatitis B. METHODS: One hundred and twenty patients with chronic hepatitis B were randomly divided into matrine treatment group (n =60) and control group (n =60). The patients of the matrine group were given intramuscularly with matrine (an alkaloid extracted from a traditional Chinese herb Radix Sophorae Flavescentis by Guangzhou Ming Xing Pharmaceu cal Factory, Guangzhou, China) of 100 mg daily for 90 days in addition to conventional liver-protective drugs in- cluding glucurone, inosine, compound vitamin B and caryophyllin. The control group received conventional liv- er-protective drugs alone. Clinical manifestations and labo- ratory parameters including liver biochemistry and serum hepatitis B virus markers were monitored before and after treatment in the two groups. RESULTS: Significant differences were seen between the two groups in terms of improvement of clinical symptoms and signs, recovery of liver functions, and serum conver- sion from hepatitis Be antigen to HBe antibody and from positive to negative serum HBV DNA (P <0.05-0.01). The result of the matrine group was more marked than that of the control group. Serious side-effects were not observed except mild pain at the site of injection of matrine in a few patients. CONCLUSION: These results indicate that intramuscular matrine may be an economical, efficacious, safe drug for the treatment of chronic hepatitis B.
基金Supported by National Natural Science Foundation of China,No.81704059
文摘BACKGROUND Ulcerative colitis(UC)is a main form of inflammatory bowel disease.Due to complicated etiology and a high rate of recurrence,it is quite essential to elucidate the underlying mechanism of and search for effective therapeutic methods for UC.AIM To investigate the effects of astragalus polysaccharides(APS)combined with matrine on UC and associated lung injury.METHODS UC was induced in rats by colon mucosal tissue sensitization combined with trinitro-benzene-sulfonic acid-ethanol.Then,the effects of the treatments of salazopyrine,APS,matrine,and APS combined with matrine on histopathological changes of lung and colon tissues,disease activity index(DAI),colon mucosal damage index(CMDI),serum endotoxin(ET)level,serum diamine oxidase(DAO)activity,the contents of tumor necrosis factor-αand interleukin-1β,and the activities of myeloperoxidase,superoxide dismutase,and malondialdehyde in lung tissues,as well as the protein expression of zonula occludens(ZO)-1,Occludin,and trefoil factor 3(TFF3)were detected in UC rats.RESULTS The treatments of salazopyrine,APS,matrine,and APS combined with matrine reduced DAI scores and improved histopathological changes of colon and lung tissues,as well as decreased CMDI scores,ET levels,and DAO activities in UC rats.Moreover,in lung tissues,inflammatory response and oxidative stress injury were relieved after the treatments of salazopyrine,APS,matrine,and APS combined with matrine in UC rats.Furthermore,the expression of ZO-1,Occludin,and TFF3 in lung and colon tissues was increased after different treatments in UC rats.Notably,APS combined with matrine exerted a better protective effect against UC and lung injury compared with other treatments.CONCLUSION APS combined with matrine exert a synergistic protective effect against UC and lung injury,which might be associated with regulating TFF3 expression.
基金supported by Science and Technology Plan Project of Beijing(No:Z151100004015194)
文摘Objective:To study the inhibitory effect of matrine on bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway. Methods:Human T24 bladder cancer cell lines were cultured and treated with different doses of matrine(0.25 mg/mL,0.5 mg/mL and 1.0 mg/mL) as well as 20 μmol/L PI3K inhibitor LY294002 for 24 h,and the cell proliferation activity,the number of invasive cells as well as the expression of p-PI3K,p-AKT,proliferation genes and invasion genes were determined. Results:Different doses of matrine could decrease the cell viability value,the number of invasive cells as well as the expression of p-PI3K,p-AKT,MMP2 and MMP9,and increase the expression of p16,p21 and p27 in dose-dependent manner; p16,p21 and p27 expression in cells of 20 μmol/L LY29002 group were significantly higher than those of 0 μmol/L LY29002 group while MMP2 and MMP9 expression were significantly lower than those of 0 μmol/L LY29002 group(P<0.05). Conclusions:Matrine can inhibit bladder cancer cell proliferation and invasion in vitro and regulate the expression of cell cycle-inhibiting molecules and invasion-related genes through PI3K/AKT signaling pathway.
基金supported by the Science and Technology Projectsof Technology Bureau of Taiyuan City(Graut No:11016203)
文摘Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly divided into A,B,C,D groups with 12 in each,group A as the normal control group and groups B.C,D as liver fibrosis models using composite modulus method with carbon tetrachloride(CCL_4).Group B was the model group,group C adopted γ— interferon lavage therapy in the second day of modeling,and group D adopted matrine lavage treatment,at 4 and8 weeks after treatment.Six rats were executed for detection of TGF- β1 and HGF,liver tissue histology and comparison fibrosis degree changes of rat liver tissue between groups.Results:Croups B,C,D showed a more significantly increased TCF- β1 at each time point compared with group A(P<0.05);Group B showed a more significantly increased TGF- β1 than groups C and D at weeks 4 and 8(P<0.05);group D showed a lowest level of TGF-β1,followed by groups C and B.HGF of group B decreased more significantly than A group at weeks 4 and 8(P<0.05);HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B(P<0.05),in which the group D showed the highest level of HGF.According to tissue histologic observation,rat liver tissue structure of group A was clear and normal,tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells;groups C and D showed a slighter liver tissue damage,cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious improvement.Conclusions:Matrine can reduce TGF- β1expression and enhance the activity of HGF,so as to realize the inhibition effect on liver fibrosis in rats.
基金Supported by special program of molecular genetics medicine for women and children's health,National Center for Women and Children's Health.China Centers for Disease Control with Grant No.FY-ZX-ZD-0059
文摘Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.
基金supported by a Grant-in-Aid for Challenging Exploratory Research(No.26670044)from the Ministry of Education,Culture,Sports,Science,and Technology of Japan(to CT)a Grant-in-Aid for a Cooperative Research Project from the Institute of Natural Medicine,University of Toyama,in 2014 and 2015(to CT)+1 种基金discretionary funds of the President of the University of Toyama,in 2014,2015,and 2016(to CT)the Natural Medicine and Biotechnology Research of Toyama Prefecture,Japan(to CT)
文摘In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness is not sufficient. We previously found a new effective compound for spinal cord injury, matrine, which induced axonal growth and functional recovery in acute spinal cord injury mice via direct activation of extracellular heat shock protein 90. Although our previous study clarified that matrine was an activator of extracellular heat shock protein 90, the potential of matrine for spinal cord injury in chronic phase has not been sufficiently evaluated. Thus, this study aimed to investigate whether matrine ameliorates chronic spinal cord injury in mice. Once daily intragastric administration of matrine(100 μmol/kg per day) to spinal cord injury mice were starte at 28 days after injury, and continued for 154 days. Continuous mat rine treatment improved hindlimb motor function in chronic spinal cord injury mice. In injured spinal cords of the matrine-treated mice, the density of neurofilament-H-positive axons was increased. Moreover, matrine treatment increased the density of bassoon-positive presynapses in contact with choline acetyltransferase-positive motor neurons in the lumbar spinal cord. These findings suggest that matrine promotes remodeling and reconnection of neural circuits to regulate hindlimb movement. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama(approval No. A2013 INM-1 and A2016 INM-3) on May 7, 2013 and May 17, 2016, respectively.
文摘A series of furoxan-based nitric oxide-releasing matrine derivatives(10a-f) were synthesized.The biological evaluation showed that compounds 10a,10b,10e and 10f had stronger cytotoxic activities than 5-fluorouracil against human hepatoma cells(HepG2) in vitro.
基金funded by the Special Fund for Forest-Scientific Research in the Public Interest(No.201304403-4)the Fundamental Research Funds for the Central Universities(2572015AA25)
文摘Matrine is a promising botanical antifungal;however, the mechanism underlying the antifungal activity is yet limited. We studied the antifungal activity of matrine and the underlying mechanism in Botryosphaeria dothidea as a model strain. Matrine strongly inhibited mycelial growth of B. dothidea in a dose-dependent manner. Matrine-treated B. dothidea showed morphological and ultrastructural alterations, including shriveled hyphae, plasmolysis, and leakage of cytoplasm related to cell membrane deterioration. In addition, matrine caused significantly high conductivity and absorbance (260 nm) in extracellular matrices and low lipid contents in B. dothidea, indicating increased membrane permeability. Lipid peroxidation showed that matrine resulted in increased malondialdehyde content while enhancing the generation of reactive oxygen species and the activities of superoxide dismutase, catalase, and peroxidase. These results showed that matrine inhibited the mycelial growth of B. dothidea by enhancing cell membrane permeability via membrane lipid peroxidation.
文摘Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、immunity liver injury of mice and chronic liver injury of rats.Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride(CCl4),thioacetamide(TAA),D-galactosamine(D-GalN),immunity hepatic injury model of mice induced by BCG and fat polysaccharide(LPS),chronic liver injury model of rats induced by CCl4 were introduced in the experiment.The serum ALT and AST were measured in acute hepatic injury experiments.Serum ALT,AST,AKP,ALB,TP,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen,hepatic hydroxyproline(HyP)of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride.Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4,TAA and D-GalN.The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment.Compared with the model group,the injection may obviously inhibited serum ALT,AST,TP,AKP,TRI,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4,elevated ALB、A/G,reduced the liver HyP,decreased the index of the liver and the spleen.The liver visual observation,the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue,restrain the liver cell damage,reduce the pseudolobuli formation.Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and chronic liver injury of rats induced by CCl4.
文摘Objective The present in vivo study was undertaken to determine whether matrine,a kind of traditional Chinese medicinal alkaloid,would relax the isolated guinea pig aortic smooth muscles,if so,to investigate the mechanism involved.Methods The concentration-dependent relaxation response to matrine was studied in phenylephrine or potassium chloride precontracted guinea pig aortic rings.Results Matrine(1×10-4 M-3.3×10-3 M)relaxed the endothelium denuded aortic rings precontracted submaximally with phenylephrine,in a concentration-dependent manner,and it's preincubation(3.3×10-3 M)produced a significant rightward shift in the phenylephrine dose-response curve,but had no effects on the potassium chloride-induced contraction.The anticontractile effect of matrine was not reduced by the highly selective ATP-dependent K+ channel blocker glibenclamide(10-5 M),the non-selective K+ channel blocker tetraethylammonium(10-3 M),as well as the β-antagonist propranolol(10-5 M).In either "normal" or "Ca2+-free" bathing medium,the phenylephrine-induced contraction was attenuated by matrine(3.3×10-3 M),indicating the vasorelaxation was due to inhibit of intracellular and extracellular Ca2+ mobilization.Conclusions The results obtained clearly demonstrated that matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with both the release of intracellular Ca2+ and the influx of extracellular Ca2+.
基金The project supported by National Natural Science Foundation of China(31570357)
文摘OBJECTIVE Experimental autoimmune encephalomyelitis(EAE),the classical animal model for multiple sclerosis(MS)is triggered by an impaired balance of T helper(Th)cells and regulatory T(Tregs)cells.Matrine(MAT),a quinolizidine alkaloid derived from the herb Radix Sophorae Flave,has been shown to ameliorate the clinical signs,inflammatory infiltration,demyelination in acute EAE rats.However,whether MAT protect from EAE by adjusting Th and Treg cells response in specific-cellular and molecular level is unknown.METHODS Herein,MAT was tested for its effects on Th1,Th2,Th17 and Treg cells in the spinal cord of EAE mice and splenocyte-extracted from EAE mice with MOG35-55-restimulated,respectively.RESULTS Our findings revealed that MAT significantly inhibit the proliferation of splenocyte,and remarkably down-regulate the differentiation of Th1/Th17 cells with decreased expressions of CD4+IFN-γ+cells and CD4+IL-17+cells in vivo and IL-17,IFN-γ,ROR-γt,T-bet in vitro,meanwhile it dramatically up-regulate the Th2/Treg cells response associated with increased levels of CD4+TGF-β+1cells and CD4+IL-10+cells in vivo and IL-4,IL-10,TGF-β1,Foxp3 and GATA3in vitro.CONCLUSION Considering the effective therapeutic effects of MAT on EAE,it′s worth to find its new values on other autoimmune diseases.
基金Supported by the Heilongjiang Provincial Education Department of Overseas Scientific Research Funded Projects(1251H006)
文摘The aim of this study was to select drugs for prevention and treatment of bovine papilloma in vitro, using bovine papilloma virus(BPV-2) infected mouse mammary epithelial(C127) cell lines as the infectious cell model system. C127 cell shapes changed with BPV infection observed under light microscopy. C127 cell shapes changed with BPV infection observed under light microscopy. PCR was used to confirm BPV infected C127 cells. mR NA levels of matrine to BPV-2 infected C127 cells were detected by RT-PCR. Apoptosis of BPV-infected C127 cells treated with matrine was analyzed by flow cytometry. Results showed that 80 μg· mL^(-1) matrine had a direct virucidal and intervention effect of BPV-2. Matrine inhibited the proliferation of BPV-infected cells. Therefore, matrine might be regarded as a therapeutic drug candidate for BPV induced bovine papilloma disease treatment in future.
基金supported by the National Natural Science Foundation of China(No. 81360111No.81660133)
文摘Objective:To investigate the effect of matrine against biofilm formation of Escherichia coli(E.coli)in the early stage.Methods:Biofilms of E.coli(ATCC25922)was induced by using a peritoneal dialysis catheter in 96-well plates.After treatment with matrine for 24 h,the formation of biofilm on the catheters was observed by scanning electron microscope.The expressions of the flagellar gene(fliC)and motility genes(motA and motB)were determined by qPCR,and the protein expression of fliC was detected by western blotting.Results:The biofilm formation of E.coli was suppressed by different concentrations(less than the minimal inhibitory concentration)of matrine,and the mRNA levels of motA and motB as well as the mRNA and protein expression levels of fliC were decreased in a dose-dependent manner.Conclusion:Matrine could inhibit biofilm formation of E.coli via downregulating the expression of motA,motB and fliC.
