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Showing papers on "Brucine published in 2018"


Journal ArticleDOI
TL;DR: Brucine inhibited triple negative breast cancer cells metastasis potentially through EMT reversion and MMP-2 and M MPs inhibition and decreased the protein and mRNA levels of mesenychmal markers such as vimentin and fibronectin.
Abstract: To examine the effect of brucine on the migration, invasion, adhesion and expressions of epithelial-to-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs) in the highly metastatic breast cancer cell lines MDA-MB-231 and Hs578-T. MDA-MB-231 and Hs578-T cells were divided to 4 groups: the control group (0.1% DMSO), and 25, 50 and 100 μmol/L brucine groups. The cell viability was determined using a CellTiter-Glo® luminescent cell viability. The scratch wound healing assay and tanswell migration assay were used to determine the migration ability of these cells treated by different concentrations of brucine. The proliferation rate, invasive potential and adhesive ability were respectively performed by colony formation assay, transwell invasion assay and adhension assay. The protein and mRNA expressions of EMT biomarkers, MMP-2 and MMP-9 were investigated by real-time reverse transcription polymerase chain reaction and Western blot. Compared with the control group, brucine had little effect on cell viability or proliferation (P>0.05), but led to a dose-dependent decrease on migration, invasion, adhension of MDA-MB-231 and Hs578-T cells (P<0.01). Furthermore, brucine increased the protein and mRNA levels of EMT markers such as E-cadherin and β-catenin in MDA-MB-231 and Hs578-T cells, and decreased the protein and mRNA levels of mesenychmal markers such as vimentin and fibronectin, as well as the expressions of MMP-2 and MMP-9 (all P<0.01). Brucine inhibited triple negative breast cancer cells metastasis potentially through EMT reversion and MMP-2 and MMP-9 inhibition.

26 citations


Journal ArticleDOI
TL;DR: Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs and showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain.
Abstract: Strychnos alkaloids (SAs) are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP). An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs) in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.

26 citations


Journal ArticleDOI
Xianpeng Shi1, Man Zhu1, Yuan Kang1, Tianfeng Yang1, Xia Chen1, Yanmin Zhang1 
TL;DR: Brucine could suppress the migration of the colorectal cancer in vitro and in vivo and the effect was associated with the inhibition of the Wnt/β-catenin signaling pathway.

22 citations


Journal ArticleDOI
TL;DR: Brucine immuno-nanoparticles combined with anti-AFP monoclonal antibodies was more effective compared with Brucine nanoparticles or brucine alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis in vivo.
Abstract: In vitro and in vivo studies have demonstrated that brucine is able to inhibit the proliferation of liver cancer cells and growth of animal tumors, and may be a promising anticancer drug. However, high toxicity, poor water solubility, short half-life, narrow therapeutic window, and similar therapeutic and toxic doses limit its clinical application in the treatment of malignant tumors. In our previous study, brucine immuno-nanoparticles were successfully prepared and added to the culture medium of liver cancer SMMC-7721 cells, and the results indicated that the brucine immuno-nanoparticles were able to target the cell membrane of liver cancer SMMC-7721 cells and significantly inhibit the proliferation, adhesion, invasion and metastasis of SMMC-7721 cells. The aim of the present study was to investigate the antitumor effect of brucine immuno-nanoparticles in vivo by establishing an in situ transplanted liver cancer in nude mice. The results indicated that in vivo application of the brucine immuno-nanoparticles resulted in temporary liver and kidney damage, and significantly reduced the α-fetoprotein (AFP) secretion of tumor cells (Bru-NP-MAb vs. the other groups; P<0.05). The brucine concentration of tumor tissues in the brucine immuno-nanoparticles group was significantly increased compared with that of the brucine nanoparticles group (Bru-NP-MAb vs. Bru-NP group or brucine group; P<0.05). The brucine immuno-nanoparticles were able to inhibit tumor growth and cluster of differentiation 34 expression and angiogenesis of tumor tissues, and induce the apoptosis of tumor cells (Bru-NP-MAb vs. Bru-NP group or brucine group; P<0.05). In conclusion, as a novel type of targeted drug, brucine nanoparticles combined with anti-AFP monoclonal antibodies was more effective compared with brucine nanoparticles or brucine alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis in vivo. Therefore, the brucine immuno-nanoparticle is a promising targeted drug for the treatment of hepatocellular carcinoma.

16 citations


Journal ArticleDOI
TL;DR: Validation results on linearity, specificity, accuracy and precision, as well as on the application to analysis ofStrychnine and brucine in six cases of suspected semen strychni poisoning demonstrate the applicability to clinical studies.

16 citations


Journal ArticleDOI
TL;DR: A simple, rapid, and sensitive liquid chromatography-mass spectrometric method was developed and validated for simultaneous determination of main bioactive ingredients in liquorice and Semen Strychni in rat plasma and the results show that this method is sensitive, accurate and robust for biological matrix analysis.
Abstract: Semen Strychni is known for its treatment of rheumatic arthritis with a low therapeutic index. Licorice contributes a lot in herb detoxification according to the traditional Chinese medicine theory. A simple, rapid and sensitive liquid chromatography–mass spectrometric method was developed and validated for simultaneous determination of main bioactive ingredients in licorice and Semen Strychni in rat plasma. Using moclobemide and cyproterone acetate as the internal standards, the analytes were pretreated via protein precipitation with methanol. An Ultimate AQ-C18 column (3.0 μm, 3.0×100 mm) was employed for chromatographic separation, combining with gradient elution. The mobile phase consisted of 0.07% formic acid and 0.12% ammonium acetate in aqueous phase (A) and acetonitrile in organic phase (B). The elution program was as follows: 0–0.5 min, 20% B; 0.5–1 min, 20–60% B; 1–7 min, 60–85% B; and 7–7.5 min, returned to 20% B, then continued to 12 min. Selected reaction monitoring was performed in both positive and negative ESI. Positive mode was adopted for detection of strychnine, brucine and moclobemide, while negative mode was used for glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, liquiritin and cyproterone acetate. The method was validated for specificity, linearity, matrix effect, recovery, precision, accuracy and stability. The results show that this method is sensitive, accurate and robust for biological matrix analysis. Moreover, the proposed method was applied to a pharmacokinetic study in Sprague-Dawley rats for investigating the mechanism of which liquorice detoxifies Semen Strychni.

15 citations


Journal ArticleDOI
Hao Zheng1, Zhe Wang1, Wenwei Liu, Hong-tao Jin1, Jinlan Zhang1 
TL;DR: A sensitive and simple rapid-resolution liquid chromatography/tandem mass spectrometry method was developed and successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats, which showed different toxicokinetics characteristics in the different groups.
Abstract: Biqi capsule is a well-known traditional Chinese medicine (TCM) formula that has been widely applied for the clinical treatment of such diseases as rheumatoid arthritis, scapulohumeral periarthritis, and cervical spondylopathy. However, there is concern regarding the toxicity of Biqi capsule due to its active ingredients, strychnine and brucine. To investigate the toxicokinetics of strychnine and brucine after the oral administration of Biqi capsule to rats, a sensitive and simple rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) method was developed to determine the levels of strychnine and brucine in rat plasma. Chromatographic separation was performed on a CAPCELL PAK C18 MG II (3.0 μm, 2.0×35 mm) column by gradient elution with acetonitrile and 0.2% formic acid as the mobile phase. The method was validated over the range of 0.25 to 250 ng/mL for strychnine and 0.025 to 25 ng/mL for brucine. The intra- and inter-day accuracies of strychnine and brucine in rat plasma were 100.3%-106.6% and 90.75%-106.1% respectively, and the precisions were within 14.2%. The established method was successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats at 0.4-, 0.8-, and 1.6-g/kg doses. The results showed different toxicokinetic characteristics in the different groups.

8 citations


Journal ArticleDOI
TL;DR: This study suggests that introduction of an oxygen to compensate for the N+ − charge could be a useful strategy for reducing hERG potency and increasing the safety margin of alkaloid‐type compounds in drug development.

7 citations


Journal ArticleDOI
Tiankun Ren1, Menglin Li1, Hao Zheng1, Wenwei Liu, Jinlan Zhang1 
TL;DR: Brucine and strychnine showed high brain penetration, so it is very important to well control the clinic dosage of BQC and manufactory quality for avoiding the side effects and obtaining good therapeutic efficacy.

6 citations


Journal ArticleDOI
TL;DR: In this article, the authors used broadband dielectric spectroscopy (BDS) for studying the drug in the super cooled and glassy state, and found the values of activation energy of the α relaxation, fragility and glass transition temperature.
Abstract: Brucine has good anti-tumor effects, on both liver cancer and breast cancer. It has bioavailability of 40.83%. Since the bioavailability of the drug is low, an alternative method to increase its bioavailability and solubility is by changing the drug into glassy form. We used Differential Scanning Calorimetry (DSC) for studying the glass forming ability of the drug. Brucine was found to be a very good glass former glass transition temperature 365 K. Based on the DSC analysis we have used broadband dielectric spectroscopy (BDS) for studying the drug in the super cooled and glassy state. BDS is an effective tool to probe the molecular dynamics in the super cooled and glassy state. Molecular mobility is found to be present even in the glassy state of this active pharmaceutical ingredient (API) which is responsible for the instability. Our aim is to study the factors responsible for instability of this API in amorphous form. Cooling curves for dielectric permittivity and dielectric loss revealed the presence of structural (α) and secondary relaxations (β and γ). Temperature dependence of relaxation time is fitted by Vogel–Fulcher–Tammann equation and found the values of activation energy of the α relaxation, fragility and glass transition temperature. Paluch’s anti correlation is also verified, that the width of the α-loss peak at or near the glass transition temperature Tg is strongly anticorrelated with the polarity of the molecule. The larger the dielectric relaxation strength Δe (Tg) of the system, the narrower is the α-loss peak (higher value of βKWW).

5 citations



Patent
14 Sep 2018
TL;DR: In this paper, an application of brucine sulphate, an antibacterial composition, and the application of the antibacteria composition, an application, and a antibacterial preparation was described.
Abstract: The invention relates to the field of medicines and discloses an application of brucine sulphate, an antibacterial composition, an application of the antibacterial composition, and an antibacterial preparation. The composition comprises brucine and brucine sulphate, and the weight ratio of the brucine to the brucine sulphate is 1:(1-20). The provided brucine sulphate and the antibacterial composition have the effects of efficiently inhibiting escherichia coli and staphylococcus aureus at the same time.