Showing papers on "Brucine published in 2014"
TL;DR: Compared with ENB based EME, the proposed IL-EME is more reliable and could provide better extraction performance for the determination of strychnine and brucine in human urine.
41 citations
TL;DR: Results indicated that high dose of Semen Strychni might induce renal injury and Radix Glycyrrhizae and Rhizoma Ligustici might work together and have effects on the elimination of strychnine and brucine.
38 citations
TL;DR: The results of this study suggested that Tm of TSL should be increased to obtain improved drug delivery efficiency to tumor.
34 citations
TL;DR: MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy and significantly increased pharmacological activities when administered by the oral route were obtained with MTAF.
Abstract: The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF) extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF). The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP). In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.
31 citations
TL;DR: A novel brucine imprinted polymer prepared on multi-walled carbon nanotubes by reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization showed enhanced accessibility to brucines and improved selective recognition property in water medium and the resulting electrochemical sensor presented good analytical performance.
31 citations
TL;DR: The results indicated that the CZE method is simple, rapid, reliable, and can be applied to determine strychnos alkaloids in traditional Chinese herbal medicines.
21 citations
TL;DR: The density functional theoretical computations were performed at the B3LYP/6-311G++(d, p) level to calculate the equilibrium geometry, vibrational wave numbers, intensities, and various other molecular properties of brucine and strychnine, which were found in satisfactory agreement with the experimental data.
19 citations
TL;DR: This study provides a practical approach for rapidly identifying complicated metabolites, a methodology that could be widely applied not only in forensic and clinically toxicological relevant cases, but also for the structural characterization of metabolites of other compounds.
Abstract: An in vivo study of Strychnos alkaloids metabolites in rats by ultra high performance liquid chromatography with linear ion trap Orbitrap MS is reported for the first time. Two major Strychnos alkaloids compounds including strychnine and brucine were investigated. To obtain optimal extraction efficiency, samples were pretreated by using an SPE plate. The structures of metabolites and their fragment ions were characterized based on the accurate mass and MSn data. Forty-seven metabolites were identified in rat urine, of which 25 were reported for the first time. Four new metabolism pathways were proposed on the basis of the identified metabolites. This study provides a practical approach for rapidly identifying complicated metabolites, a methodology that could be widely applied not only in forensic and clinically toxicological relevant cases, but also for the structural characterization of metabolites of other compounds.
15 citations
TL;DR: Brucine can inhibit the proliferation of human lung cancer cell line PC-9 mainly by blocking the cell cycle at G0/G1 via down-regulating the expression of Cyclin D1, Cyclin E.
Abstract: Background and objective It has been proven that Cyclin D1 and Cyclin E are the important positive regulators of cell cycle, they are closely related to the tumor proliferation. The aim of this study is to explore the relationship between Brucine and the proliferation in human lung cancer cell line PC-9, and the effect of it on the expression of Cyclin D1 and Cyclin E. Methods PC-9 cells were divided to 4 groups: the normal control group, the DMSO control group (2‰), the 150 μM Brucine group, and the 300 μM Brucine group. The proliferation rate of PC-9 cells was determined by The CellTiter-Glo Luminescent Cell Viability Assay and Colony Formation assay. The change of cell cycle was detected by Flow cytome try. Expressions of cell cycle regulators Cyclin D1, Cyclin E mRNA were determined by qRT-PCR. Protein expression of cell cycle regulators Cyclin D1, Cyclin E were determined by Western blot. Results Compared with the control, Brucine remarkably inhibited the proliferation of PC-9 cells in a dose- and time-dependent manner (P<0.01); Flow cytome try showed that Brucine blocked the cell cycle of PC-9 cells at G0/G1, and the differences were statistically significant (P<0.01); qRT-PCR showed that the expression of Cyclin D1, Cyclin E mRNA were down-regulated; Western blot showed that the protein expression of Cyclin D1, Cyclin E were down-regulated. Conclusion Brucine can inhibit the proliferation of human lung cancer cell line PC-9 mainly by blocking the cell cycle at G0/G1 via down-regulating the expression of Cyclin D1, Cyclin E.
DOI: 10.3779/j.issn.1009-3419.2014.06.02
11 citations
TL;DR: The first investigation of in vivo metabolism of brucine in rats using LC-ESI-ion trap-TOF-MS provides basic information for better understanding of the pharmacological and toxicological activities of Brucine-containing medicines.
Abstract: Background: Brucine is a widely prescribed glycine antagonist, but a complete understanding of its metabolic pathway is still lacking. The present work represents the first investigation of in vivo metabolism of brucine in rats using LC–ESI-ion trap-TOF-MS. Results: A total of 12 Phase I and five Phase II metabolites were tentatively identified. Brucine can be metabolized by hydrolysis, demethylation and methoxylation, in addition to diverse oxidations in a Phase I manner followed by glucuronidation in Phase II metabolism. Both the renal and biliary routes were observed for the excretion of brucine and its metabolites. Conclusion: Our results update the metabolism and disposition data on brucine, which provides basic information for better understanding of the pharmacological and toxicological activities of brucine-containing medicines.
9 citations
TL;DR: The proposed method was successfully applied to determine non-protein-bound strychnine and Bru, and the analysates concentration remained stable in rabbit muscle and synovial fluid after topical application of total Strychnos alkaloid patches, which indicated that totalStrychno alkaloids patches could substitute for the traditional oral administration of Semen Stychni.
Abstract: Semen Strychni, a known toxic drug in Chinese pharmacopoeia, is notable for its therapeutic effects on local muscle and joint pain. However, oral administration can be risky. Topically administered drugs accumulate in the topical muscles and knee joints without any major increase in plasma levels; only non-protein-bound drugs in the biological fluids of target tissues are effective for therapeutic effects. A sensitive and rapid ultra performance liquid chromatography - mass spectrometry (UPLC-MS) method coupled with a microdialysis technique was developed to determine the non-protein-bound strychnine (Str) and brucine (Bru) in rabbit muscle and synovial fluid microdialysate. The UPLC separation was carried out using a 1.7μm BEH C18 column (50 mm × 2.1 mm) with a mobile phase consisting of methanol: water (29.5:70.5, v/v) with 0.1% formic acid and 20 mM ammonium acetate in water. The method was validated at concentrations ranging from 0.58 ng/ml to 467.20 ng/ml for Str and from 0.42 ng/ml to 422.40 ng/ml for Bru. Intra-day and inter-day accuracy ranged from 99.1% to 103.2% for Str and from 95.8% to 108.8% for Bru with intra-day and inter-day precision within 9.7%. The proposed method was successfully applied to determine non-protein-bound Str and Bru, and the analysates concentration remained stable in rabbit muscle and synovial fluid after topical application of total Strychnos alkaloid patches, which indicated that total Strychnos alkaloid patches could substitute for the traditional oral administration of Semen Strychni. Copyright © 2013 John Wiley & Sons, Ltd.
TL;DR: In this article, the role of the additives on the crystallization of brucine hydrates was studied, and a new, kinetically favored, Brucine 3.86-hydrate was obtained from solutions containing diethanolamine, adenosine, and urea.
Abstract: Up to now, three brucine hydrates are known, brucine di-, tetra-, and 5.25-hydrate. All of them were obtained from solutions containing the additive diethanolamine, adenosine, and urea, respectively. Studying the role of the additives on crystallization of the brucine hydrates, we obtained a new, kinetically favored brucine 3.86-hydrate. In crystals of brucine 3.86-hydrate, large 15- and 16-membered water clusters of cuboidal topology are encapsulated in cages formed between honeycomb-like brucine layers. Dehydration of the brucine hydrate leads to formation of the known anhydrous brucine, giving insight into a mechanism of the dehydration process, in which a shift of brucine ribbons in the honeycomb-like layers leads to an openining of channels and water release. A collapse of brucine layers after the water release results in formation of the common anhydrous brucine. The anhydrous brucine undergoes a phase transition at 249 K in the cooling mode and at 277 K in the heating mode. The phase transition is ...
TL;DR: It is concluded that brucine can efficiently inhibit cell growth and block THP-1 cells in G0/G1 phase and related to the inhibition of BCL-2 and activation of BAX.
Abstract: This study was aimed to investigate the inducing-apoptosis effect of brucine on human monocytic leukemia cell line THP-1 cells and its possible mechanism. The inhibition effect of brucine on growth of THP-1 cells was measured by CCK-8 method. Morphological changes of THP-1 cells treated with brucine was detected by acridine orange/ethidium bromide (AO/EB)double staining. Annexin-V/PI double labeling method was used to assay the apoptosis rate of THP-1 cells. The effect of brucine on THP-1 cell cycle distribution was detected by PI single staining. RT-PCR was used to detect the expression of BCL-2 and BAX. The results showed that the brucine could inhibit the THP-1 cell growth in concentration and time-dependent manners at the range of 50 to 400 µg/ml. The cells stained with AO/EB revealed that the brucine induced the nuclear chromatin condensation. After the THP-1 cells were treated with brucine of 400µg/ml for 48 hours, most nucleic were stained as orange-red, and condensed, displaying the late apoptotic cell morphology. Annexin-V/PI detection showed that brucine could induce apoptosis of THP-1 cells in a concentration-dependent manner. Compared with the control group, more cells in brucine-treated group were arrested at G0/G1 phase in a concentration-dependent manner. RT-PCR detection revealed that the expression of BCL-2 was down-regulated strikingly and BAX was up-regulated. It is concluded that brucine can efficiently inhibit cell growth and block THP-1 cells in G0/G1 phase. The mechanism of THP-1 cell apoptosis induced by brucine may be related to the inhibition of BCL-2 and activation of BAX.
Journal Article•
TL;DR: It is suggested that brucine in combination with gemcitabine showed supra-additive anticancer effects in MDA MB-231 cells and warrants further in-vivo studies in experimental animal models.
Abstract: Combination of natural compounds and cytotoxic drugs represents a logical therapeutic approach for breast cancer. Brucine, a natural plant alkaloid is reported to possess cytotoxic, anti-inflammatory and anti-cancer activities. Gemcitabine is a nucleoside analog, commonly used in the treatment of several solid tumors, including breast cancer. In the present study we have examined the anticancer effect of brucine and gemcitabine on MDA MB-231 human breast cancer cells. Cell proliferation was assessed using MTT assay. Soft agar assay was used to evaluate the in-vitro clonogencity of MDA MB-231 cells. Cell migration was determined by in-vitro scratch assay and expression of p65 (NF-kB subunit) was evaluated by western blot analysis. Combination treatment with brucine and gemcitabine resulted in a significant inhibition of cell proliferation than either brucine or gemcitabine alone. Cells treated with combination of brucine and gemcitabine showed additive inhibition in colony formation and cell migration than treated with individual agents. The cells treated with brucine at 300 µM showed a significant decrease in p65-NF-kB expression but in combination treatment there was no additive inhibition of p65 expression compared to brucine treated cells. Overall, our results suggested that brucine in combination with gemcitabine showed supra-additive anticancer effects in MDA MB-231 cells and warrants further in-vivo studies in experimental animal models.
TL;DR: In this paper, the antibacterial activity of Strychnos nux vomica leaves showed inhibitory effects on selective bacteria which could be used to control these microbes, but Salmonella typhimurium survived the inhibition.
Abstract: Strychnos nux vomica is a non edible tree with a strong content of two poisonous alkaloids, strychnine and brucine. Qualitative phytochemical analysis and antimicrobial activity of the aqueous methanolic extract of its leaves were studied. Alkaloids, triterpenes, oils & fats, phenol, tannins and flavonoids were present. Escherichia coli Enterobacter, Staphylococcus aureus, and Pseudomonas showed susceptibility but Salmonella typhimurium survived the inhibition. Minimal inhibitory concentration of the extract for E. coliafter an overnight incubation was found to be 0.25 mg. In the present study the antibacterial activity of Strychnos nux vomica leaves showed inhibitory effects on selective bacteria which could be used to control these microbes.
01 Jan 2014
TL;DR: In this article, a simple and cost effective spectrophotometric method was described for the determination of Imipenem in pure form and in pharmaceutical formulations, which is based on the formation of colored chromogen when the drug reacts with brucine and sodium periodate in acidic medium.
Abstract: A simple and cost effective spectrophotometric method was described for the determination of Imipenem in pure form and in pharmaceutical formulations. The method is based on the formation of colored chromogen when the drug reacts with brucine and sodium periodate in acidic medium. This method was applied for the determination of drug contents in pharmaceutical formulations and enabled the determination of the selected drug in microgram quantities (0.5 to 3.0 mL). No interferences were observed from excipients and the validity of the method was tested against reference method. The colored species has an absorption maximum at 520 nm for Imipenem and obeys beer’s law in the concentration range 0.02-0.12 mg/mL of Imipenem. The apparent molar absorptivity was 61X10-5 and sandell’s sensitivity was 7x10-4. The slope is 0.0230 ± 0.0008, the intercept of the equation of the regression line is 0.0230 ± 0.0008. The optimum experimental parameters for the reaction have been studied and the validity of the described procedure was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed method was successfully applied for the determination of Imipenem in pharmaceutical formulations.
Patent•
01 Oct 2014
TL;DR: In this article, the authors proposed a method for extracting brucine and strychnine simultaneously, which includes the following treatment steps of: adding acidified water into bruised crude powder, then, centrifuging after carrying out continuous countercurrent ultrasonic extraction to obtain leach liquor, regulating the PH value to 9-10, directly passing through pre-treated macroporous adsorption resin, using same amount of distilled water to flush, and then, using 8-10 BV of 70-80% alcohol to elute at a flow speed of 10 mL/
Abstract: The invention relates to a method for extracting brucine and strychnine simultaneously. The method comprises the following treatment steps of: adding acidified water into brucine crude powder, then, centrifuging after carrying out continuous countercurrent ultrasonic extraction to obtain leach liquor, regulating the PH value to 9-10, directly passing through pre-treated macroporous adsorption resin, using same amount of distilled water to flush, then, using 8-10 BV of 70-80% alcohol to elute at a flow speed of 10 mL/min, concentrating eluant under reduced pressure until volume of the eluant is 1/8-10 the original vaolume of the eluant, adding 10% alcohol sulfate liquor, standing to obtain brucine sulfate, repeatedly crystallizing twice to obtain brucine with purity greater than 98%; alkalifying crystallized mother liquor, adding 10% hydrochloric acid alcohol liquor, and standing to obtain strychnine hydrochloride. The method disclosed by the invention adopts a modern extracting technology to carry out continuous countercurrent ultrasonic extraction to extract brucine, has the advantages of being simple in process, gentle in reaction condition, short in extracting time and high in selectivity, low in extracting cost, and is suitable for industrial production.
TL;DR: In this paper, the effect of particle size on the quality uniformity and in vitro release performance of Strychnos nux-vomica powder with different particle sizes was explored.
Abstract: To explore the effect of particle size on the quality uniformity and in vitro release performance of Strychnos nux-vomica powder, seven samples of Strychnos nux-vomica powder with different particle sizes were prepared. Microstructures and particle sizes were analyzed, and high performance liquid chromatography (HPLC) was used to test the contents and in vitro release performances of brucine and strychnine in the samples. Results showed that the contents and the in vitro release rates of brucine (or strychnine) in different samples were different since there are different proportions of endosperms to epidermal cells in Strychnos nux-vomica powder with different particle sizes. Brucine and strychnine in each sample were promptly released in the first ten minutes and their cumulative release rates were higher than 70% after ten minutes. Eighty minutes later, the cumulative release rate tended to be a constant. Considering the quality uniformity and safety of Strychnos nux-vomica powder used as traditional Chinese medicine, it would be better to control the particle size of Strychnos nux-vomica powder between 100 and 140 mesh in which the maximum cumulative release rate in vitro of brucine and strychnine can be relatively low within this range.
TL;DR: In this paper, a capillary electrophoresis method was developed for the determination of brucine in strychnos, and the analytical conditions were optimized after investigating the effects pH and concentration of buffer.
Abstract: A capillary electrophoresis method has been developed for the determination of brucine in strychnos. The analytical conditions were optimized after investigating the effects pH and concentration of buffer. Under optimized conditions (20 mmol/L NaH2PO4-Na2HPO4, pH=6.0, 20 kV, 254 nm,), the brucine was separated in 5 min.
Dissertation•
01 Jan 2014
TL;DR: Li et al. as mentioned in this paper used Brucine N-oxide as a nucleophilic organic catalyst in the MBH reaction of alkyl vinyl ketone and showed that the Noxide activated vinyl ketones provided enolates through the conjugate addition.
Abstract: Li, Jian-Yuan Ph.D., Purdue University, December 2014. The Modification of Brucine Derivatives as Chiral Ligands and Its Application in the Asymmetric Synthesis. Major Professor: Robert Minto. The modification of brucine derivatives as chiral ligands and the use of a multifaceted chiral ligand, brucine diol, under different reaction conditions to produce various optical isomers is described. In Chapter 1, the generation of a number of brucine derivatives is described. Taking the advantage of brucine-diol’s excellent molecular recognition capability for multiple organic functional groups, we focused on the synthetic modifications of brucine-diol and the synthesis of brucine N-oxide. We also produced various brucine derivatives with different functional moieties in good yields and selectivities. In Chapter 2, we described the investigation of brucine N-oxide catalyzed MoritaBaylis-Hillman (MBH) reaction of alkyl/aryl ketones. Brucine N-oxide was used as a nucleophilic organic catalyst in the MBH reaction of alkyl vinyl ketone. In addition, asymmetric MBH reactions of alkyl vinyl ketones with aldehydes were investigated using a dual catalysis of brucine N-oxide and proline. In this dual catalyst system, proline was found to form iminium intermediates with electron-deficient aryl aldehydes, while the Noxide activated vinyl ketones provided enolates through the conjugate addition. Our dual catalysis approach also allowed the development of MBH reaction of aryl vinyl ketones.