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Showing papers on "Brucine published in 2013"


Journal ArticleDOI
TL;DR: The study suggests that brucine potently suppresses angiogenesis by targeting VEGFR2 activation and may be a viable drug candidate in anti-angiogenesis and anti-cancer therapies.

58 citations


Journal ArticleDOI
TL;DR: The liquid chromatography-tandem mass spectrometry method was successfully applied in analysis of 170 cases of suspected herbal poisoning, with aconitum alkaloids, sophoridine, oxymatrine, cytisine, N-methylcytisine and strychnos alkaloid being detected in 53, 42, 18, and 6 cases, respectively.

50 citations


Journal ArticleDOI
TL;DR: It is demonstrated that brucine dramatically repressed HepG2 and SMMC-7721 HCC cell migration with few cytotoxic effects and the inhibition of the HIF-1 pathway is implicated in the anti-metastasis activity of brucines.

44 citations


Journal ArticleDOI
15 Nov 2013-Talanta
TL;DR: A mixed matrix membrane (MMM), based on carbon nanotubes and hollow fiber, was prepared and combined with solid phase microextraction (SPME) mode to determine strychnine and brucine in urine and shows comparable results against reference methods and is a simple, green, and cost-effective microextracted technique.

42 citations


Journal ArticleDOI
Lei Zheng1, Xiaoli Wang1, Wenjuan Luo1, Yingzhuan Zhan1, Yanmin Zhang1 
TL;DR: Brucine is effective against Lo Vo cells proliferation, and promotes LoVo cells death via apoptosis, which reveals functional interplay among a series of pathway that are deregulated in cancer and suggest that their simultaneous targeting by Brucine could result in efficacious inhibition on cancer cells.

36 citations


Journal ArticleDOI
TL;DR: It is indicated that brucine prevents lipid peroxidation and hepatic cell damage and also protects the antioxidant system in DENA-induced hepatocarcinogenesis.

36 citations


Journal ArticleDOI
Xin Li1, Kai Wang1, Wei Wei1, Yong-yu Liu1, Lu Gong1 
TL;DR: The results suggest that brucine has the potential to interact with a wide range of xenobiotics and endogenous chemicals especially CYP3A4 substrates.

25 citations


Journal ArticleDOI
TL;DR: The results suggest that brucine could inhibit angiogenesis and be a useful therapeutic candidate for colon cancer intervention.
Abstract: Angiogenesis plays an important role in colon cancer development. This study aimed to demonstrate the effect of brucine on tumour angiogenesis and its mechanism of action. The anti-angiogenic effect was evaluated on the chicken chorioallantoic membrane (CAM) model and tube formation. The mechanism was demonstrated through detecting mRNA and protein expressions of VEGFR2 (KDR), PKCα, PLCγ and Raf1 by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB), as well as expressions of VEGF and PKCβ and mTOR by ELISA and WB. The results showed that brucine significantly reduced angiogenesis of CAM and tube formation, inhibited the VEGF secretion and mTOR expression in LoVo cell and down-regulated the mRNA and phosphorylation protein expressions of KDR, PKCα, PLCγ and Raf1. In addition, the effects of brucine on KDR kinase activity, viability of LoVo cell and gene knockdown cell were detected with the Lance™ assay, WST-1 assay and instantaneous siRNA. Compared to that of normal LoVo cells, the inhibition on proliferation of knockdown cells by brucine decreased significantly. These results suggest that brucine could inhibit angiogenesis and be a useful therapeutic candidate for colon cancer intervention.

18 citations


Journal ArticleDOI
Ji-Xin Tian1, Can Peng1, Lei Xu1, Yuan Tian1, Zunjian Zhang1 
TL;DR: The structural elucidations of these metabolites were achieved by comparing the changes in accurate molecular masses, calculating chemical component using Formula Predictor software and defining sites of biotransformation based upon accurate MS(n) spectral information.
Abstract: In this report, the in vitro metabolism of Strychnos alkaloids was investigated using liquid chromatography/high-resolution mass spectrometry for the first time. Strychnine and brucine were selected as model compounds to determine the universal biotransformations of the Strychnos alkaloids in rat liver microsomes. The incubation mixtures were separated by a bidentate-C18 column, and then analyzed by on-line ion trap/time-of-flight mass spectrometry. With the assistance of mass defect filtering technique, full-scan accurate mass datasets were processed for the discovery of the related metabolites. The structural elucidations of these metabolites were achieved by comparing the changes in accurate molecular masses, calculating chemical component using Formula Predictor software and defining sites of biotransformation based upon accurate MS(n) spectral information. As a result, 31 metabolites were identified, of which 26 metabolites were reported for the first time. These biotransformations included hydroxylation, N-oxidation, epoxidation, methylation, dehydrogenation, de-methoxylation, O-demethylation, as well as hydrolysis reactions.

17 citations


Journal ArticleDOI
TL;DR: The anti-proliferative activity of SN-extract is associated with apoptosis, which is likely due to the presence of alkaloids, strychnine and brucine, which have been identified by MALDI-TOF-MS and RP-HPLC analysis.
Abstract: Multiple myeloma (MM) is an incurable B cell neoplasm causing significant morbidity and mortality. Despite recent advances in the MM-treatment, the disease still remains incurable; necessitating a search for new therapeutic agents. Therefore, Strychnos nux-vomica L. root extract (SN) was screened using the human MM-cell line, U266B1. SN-extract demonstrated anti-proliferative effect in a time- and dose-dependent manner. Morphological studies, cell cycle analysis by FACS indicate apoptosis. Furthermore, assessment of signaling molecules like IL-6 (interleukin-6) and CD-138 (Sydencan-1) confirmed apoptosis. The anti-proliferative activity of SN-extract is associated with apoptosis, which is likely due to the presence of alkaloids, strychnine and brucine, which have been identified by MALDI-TOF-MS and RP-HPLC analysis

16 citations


Journal ArticleDOI
TL;DR: The results of this study indicated that transdermal administration might be beneficial for the sustained efficacy and reduced toxicity of brucine.

Journal ArticleDOI
TL;DR: Brucine‑induced apoptosis in U266 cells occurs via the JNK signaling pathway and phosphorylation of c-Jun, and appears to have an effect on apoptotic effect in a dose- and time-dependent manner.
Abstract: The aim of this study was to investigate the mechanism of the apoptotic effect of brucine on human multiple myeloma (MM) cells. U266 cells (5x104) were plated in the presence or absence of brucine (0, 0.05, 0.1, 0.2 and 0.4 mg/ml) in 96‑well culture plates for 24‑72 h. The anti-proliferative response to brucine was assessed by MTT assay. Analysis of the cell cycle of U266 cells treated with or without brucine was performed using flow cytometry. The expression change of c-Jun following treatment with brucine or brucine plus the c-Jun N-terminal kinase (JNK)-specific inhibitor SP600125 was detected using RT-PCR. Brucine appeared to have an effect on apoptosis in a dose- and time‑dependent manner. Cell cycle analysis using flow cytometry revealed the accumulation of cells at the sub-G0/G1 phase. The apoptotic rates were 4.137, 10.55, 12.31, 27.67 and 29.67% (0, 0.05, 0.1, 0.2, 0.4 mg/ml brucine, respectively; P<0.01). The gray scale values were 0.7961 ± 0.007 and 0.4683 ± 0.003 (mRNA expression of c-Jun of U266 cells with or without SP600125, respectively). Concentrations of ≤ 0.4 mg/ml brucine induced apoptosis in U266 cells. Thus, brucine‑induced apoptosis in U266 cells occurs via the JNK signaling pathway and phosphorylation of c-Jun.

Journal ArticleDOI
Jie Liu1, Lingxi Yang1, Kai Zhang1, Kunjing Li1, Xianli Wu1, Baoxian Ye1 
TL;DR: In this article, a simple and reliable electrochemical sensor based on poly(DL-aspartic acid)-modified glassy carbon electrode was proposed for direct determination of brucine.
Abstract: A simple and reliable electrochemical sensor based on poly(DL-aspartic acid)-modified glassy carbon electrode was proposed for direct determination of brucine. The electrochemical character of brucine on this sensor was carefully and systematically studied by cyclic voltammetry. Some kinetic parameters were calculated and a reasonable reaction mechanism for brucine at the poly(DL-aspartic acid)/GCE was also proposed. Meanwhile, a new electroanalytical method for determination of brucine was proposed with a highly sensitive detection limit of 3 × 10−8 mol L−1 (S/N = 3) and a wide linear range of 5.0 × 10−8 to 9.0 × 10−5 mol L−1. More importantly, this sensor exhibited good stability and excellent reproducibility in the response for brucine.

Journal ArticleDOI
TL;DR: Since brucine has severe central nervous system toxicity, this study indicated that SLS-n could considerably improve the therapeutic index of brucines.
Abstract: Objective: To improve the therapeutic index of brucine, the novel stealth liposomes (SLS-n), composed of naturally unsaturated and hydrogenated soy phosphatidylcholines, with significant difference of phase transition temperature, were developed to encapsulate brucine.Methods: Brucine-loaded stealth liposomes with different lipid compositions were prepared and characterized for their entrapment efficiency (EE), particle size, zeta potential and in vitro drug release profile. Tissue distribution after intravenous administration of different brucine formulations was further compared in tumor-bearing mice.Results: Compared with the conventional stealth liposomes composed of SPC (SLS-s) or HSPC (SLS-h), EE and zeta potential of SLS-n were increased slightly, and the size was decreased slightly. The results of drug release showed that SLS-n were more stable than SLS-s. After intravenous administration, tumor AUC in SLS-s, SLS-n and SLS-h treated animals were 1.33, 1.72 and 2.59-fold higher than in mice treated...

Journal ArticleDOI
TL;DR: In this article, the quaternary mixture of potassium laurate (KL)/potassium sulfate (k2SO4)/1-undecanol (UndeOH)/water with brucine was used to construct the cholesteric helical arrangement.
Abstract: Lyotropic cholesteric liquid crystalline phases were prepared by doping the quaternary mixture of potassium laurate (KL)/potassium sulfate (K2SO4)/1-undecanol (UndeOH)/water with brucine. The phase diagram was constructed as a function of the brucine concentration. Three cholesteric phases were identified: cholesteric biaxial, calamitic uniaxial, and discotic uniaxial. It was observed that there is a critical brucine concentration (X* b ) to cholesterize the nematic host phase when the mixture is confined in a thin sample holder, below which the cholesteric helical arrangement is not achieved. The helical twisting power of brucine was calculated as 12.12 ± 0.40 μm−1.

Journal ArticleDOI
TL;DR: In this paper, a method for the chromatographic determination of strychnine and brucine in various herbal/ayurvedic sample preparations, homeopathic medicines, containing Nux-vomica, seeds of Nux vomica as well as in spiked serum and real urine samples are described.
Abstract: Nux-vomica is a tropical plant that contains two ergot alkaloids i.e. strychnine and brucine which have pharmaceutical and toxic properties. In some places, for example in India, Nux-vomica is used in ayurvedic preparations in homeopathic medicine. As both compounds are toxic monitoring is required. In this work a method for the chromatographic determination of strychnine and brucine in various herbal/ayurvedic sample preparations, homeopathic medicines, containing Nux-vomica, seeds of Nux-vomica as well as in spiked serum and real urine samples are described. The method involves a direct injection micellar liquid chromatography technique that was optimised under ICH guidelines. Optimum conditions are a mobile phase composed by 0.10 M SDS-pentanol 4% (v/v)-NaH2PO4 buffered at pH 3 with UV detection at 258 nm, flow rate of 1 mL min−1, and temperature 25 °C. Under these conditions strychnine and brucine were analyzed in 15 and 11 min, respectively. Validation studies using ICH guidelines were performed to show that the proposed method was linear (r2 > 0.9997), with LODs (0.18 and 0.09) and LOQs (0.69 and 0.35), for strycnine and brucine, respectively. Repeatability intra- and inter-day was below of 2.50. The developed method can be useful for analyzing strychnine and brucine for quality control and other related forensic and clinical cases.

Journal Article
TL;DR: Brucine has antitumor effect on many kinds of tumor cells both in vitro and in vivo by various mechanisms, including apoptosis, anti-angiogenesis, and reversal of tumor cell multidrug resistance.
Abstract: OBJECTIVE:To review advances of the anti-tumor effect and the involved mechanisms of brucineMETHODS:The related literature of anti-tumor effect of brucine was retrieved in PubMed and cnki from 1992-01-2012-01Key words were brucine and anti-tumor effect,and 126articals were obtainedThe included criteria:1) Anti-tumor effect of brucine2) Anti-tumor mechanism of of brucineThirty documents were reviewed according to the inclusion criteriaRESULTS:Brucine has antitumor effect in vitro and in vivoThe current studies found that brucine has growth inhibitory effects on hepatoma cell line SMMC 7221,Heps and H22Moreover,brucine can inhibit human breast cell line MDA-MB-231and MCF-7,human chronic myeloid leukemia cell line K562cells and multiple myeloma(MM) cell line U266,etcThe anti-tumor mechanism of brucine involves apoptosis,anti-angiogenesis,decreasing VEGF and TNF-αexpression,increasing IL-12expression and reversal of tumor cell multidrug resistanceCONCLUSION:Brucine has antitumor effect on many kinds of tumor cells both in vitro and in vivo by various mechanisms

Journal ArticleDOI
Dai Li-Bo1, Yan Miao1, Li Huande1, Fang Pingfei1, Wang Feng1, Deng Yang1 
TL;DR: This validated method was successfully applied to bidirectional transport study of moclobemide blood-brain barrier permeability and was validated from LLOQ to 1980 ng/mL with a coefficient of determination greater than 0.999.
Abstract: A simple and sensitive analytical method based on ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for determination of moclobemide in human brain cell monolayer as an in vitro model of blood-brain barrier. Brucine was employed as the internal standard. Moclobemide and internal standard were extracted from cell supernatant by ethyl acetate after alkalinizing with sodium hydroxide. The UPLC separation was performed on an Acquity UPLC(TM) BEH C18 column (50 × 2.1 mm, 1.7 µm, Waters, USA) with a mobile phase consisting of methanol-water (29.5:70.5, v/v); the water in the mobile phase contained 0.05% ammonium acetate and 0.1% formic acid. Detection of the analytes was achieved using positive ion electrospray via multiple reaction monitoring mode. The mass transitions were m/z 269.16 → 182.01 for moclobemide and m/z 395.24 → 324.15 for brucine. The extraction recovery was 83.0-83.4% and the lower limit of quantitation (LLOQ) was 1.0 ng/mL for moclobemide. The method was validated from LLOQ to 1980 ng/mL with a coefficient of determination greater than 0.999. Intra- and inter-day accuracies of the method at three concentrations ranged from 89.1 to 100.9% for moclobemide with precision of 1.1-9.6%. This validated method was successfully applied to bidirectional transport study of moclobemide blood-brain barrier permeability.

Journal Article
Chen Yong1
TL;DR: The absorption of brucine in Caco-2 cell monolayer model was well and the passive transference was its main intestinal absorption mechanism, and medium pH had important effect on the transport of Brucine.
Abstract: Objective: To study the absorption mechanism of brucine in vitro and its transport interaction with liquiritin in Caco-2 cell monolayer model.Methods: The cumulative transport concentration(TRcum),apparent permeability coefficient(PappB→A and PappA→B) of brucine were determined after Caco-2 cell monolayer model were treated by brucine and combined with liquiritin.The effects of drug concentration,conveying time,P-glycoprotein inhibitor verapamil and medium pH value on the transport of brucine in Caco-2 cell monolayer model were also investigated.Results: The Papp value of brucine was larger than 10-6cm/s,and the ratio of Papp B→A versus Papp A→B was less than 1.5.The co-treatment of brucine combined with liquiritin increase the ratio of Papp B→A versus Papp A→B,whereas the co-treatment of brucine combined with verapamil decreased the ratio of Papp B→A versus Papp A→B.Moreover,the Papp A→B in medium pH6.0 was less than that in medium pH7.4.Conclusion: The absorption of brucine in Caco-2 cell monolayer model was well and the passive transference was its main intestinal absorption mechanism.P-glycoprotein and liquiritin inhibited the absorption of brucine,and medium pH had important effect on the transport of brucine.

Patent
04 Dec 2013
TL;DR: In this paper, the contents of brucine and strychnine in the blood plasma and urine of a human body through a CE-TOF/MS method, Berberine hydrochloride is treated as an internal standard substance and all components are well separated under optimal conditions.
Abstract: The invention discloses a technology for determining the contents of brucine and strychnine in the blood plasma and urine of a human body through a CE-TOF/MS method Berberine hydrochloride is treated as an internal standard substance, all components are well separated under optimal conditions, and the sensitivity of the method is high Compared with an LC-MS method, the CE-TOF/MS method used in the invention has the advantages of improved component separation, and reduced consumption of an organic solvent when a same sensitivity is realized; and compared with an HPLC method and a CE-DAD method, the CE-TOF/MS method has the advantages of improved sensitivity, provision of accurate molecular weights of detection components, and realization of the qualitation of unknown components

Journal Article
TL;DR: In this paper, the processing technology parameters of Strychnos nux-vomica heated with sand were optimized in order to control quality of S.nux-veomica effectively.
Abstract: Objective:To optimize processing technology parameters of Strychnos nux-vomica heated with sand,in order to control quality of S.nux-vomica effectively.Method:With the content of brucine and strychnine as indexes,orthogonal test was used to evaluate effect of oil-sand degree,sand-material ratio,frying temperature and time on processing technology parameters of S.nux-vomica.Result:Optimum processing technology parameters were as followings:medium sand(300-600 μm),sand-material ratio 7∶ 1,frying temperature(190±5) ℃,frying time 4 min.Conclusion:Optimized processing technology was suitable and feasible,it was suitable for mass production.

Journal ArticleDOI
TL;DR: The study has provided a novel chemoconvulsant model of seizures induced by brucine, and established an appropriate method to develop the model that had not been found in previous literature review.
Abstract: Object: Strychnine has been reported to develop seizure models. As its analogue, brucine may also have such property. The aim of the study was to create a chemoconvulsant model of seizures by fractionated administration of brucine. Methods: Healthy male Sprague-Dawley rats (n=140) were allocated randomly into three groups: experimental groupi¼Œ normal saline control group and alcohol control group. Rats in experimental group were then randomly divided into six groups during the kindling process: three of the six subgroups were single-dose subgroups, while another three were fractionated-dose subgroups. Rats from three single-dose subgroups (n=20 for each subgroup) received single injection of brucine at three various dose levels (91 mg/kg, 100 mg/kg and 110 mg/kg, respectively); rats from the other three fractionated-dose subgroups (n=20 for each subgroup) received fractionated injections of brucine by three times with one third of the total dose each time. Rats from normal saline and alcohol control group were given normal saline and solvent injection (n=10 for each group). Seizure frequency and intensity (rated as stage 1-5 according to Racine scale), duration and electroencephalographic activity were recorded. Seizures were observed in all single-dose and fractionated-dose subgroups. Results: As dose increased, higher frequency and intensity of seizures were observed. At the dose of 110mg/kg, all rats died after stage 5 seizures in both single and fractionated dose subgroups. At doses of 91mg/kg and 100mg/kgi¼Œin single-dose subgroups, 75.00-95.00% rats were observed stage 5 seizures, but the mortality was 75.00%-95.00%; In fractionated-dose subgroups, 50.00%-100.00% rats were observed stage 5 seizures, while the mortality was 0.00%-30.00%. Conclusion: The study has provided a novel chemoconvulsant model of seizures induced by brucine, and established an appropriate method to develop the model that had not been found in previous literature review.

Journal ArticleDOI
TL;DR: In this article, the preparation of strychnine and brucine from a crude extract of Strychnos nuxvomica L. has been successfully performed for the first time using pH-zone- refining countercurrent chromatography.
Abstract: Preparative separation of strychnine and brucine from a crude extract of Strychnos nuxvomica L. has been successfully performed for the first time using pH-zone- refining counter-current chromatography. The experiment was performed with a two-phase solvent system composed of n-hexane–ethyl acetate–i-propanol–water (1: 3: 1.5: 4.5, v/v) where triethylamine (10 mM) was added to the upper stationary phase as a retainer and hydrochloric acid (5 mM) was added to the mobile phase as an eluter. From 1.5 g of the crude extract, 176 mg strychnine, and 480 mg brucine were obtained in a single run. The purities of these compounds were 95.1% and 97.0%, respectively, as determined by HPLC. The structures of the isolated compounds were confirmed by electron ionization-mass spectrometer (EI-MS) and 1H NMR.