| In vitro: |
| Int J Biol Macromol. 2015 Jun;77:92-8. | | Cytotoxicity and DNA interaction of brucine and strychnine-Two alkaloids of semen strychni.[Pubmed: 25796448] |
METHODS AND RESULTS:
The cytotoxicities of the two alkaloids strychnine and Brucine from the seed of Strychnos nux-vomica and their interaction with DNA were investigated. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrasolium bromide (MTT) assay was used to examine the growth inhibitory effects of these alkaloids on Vero cells after 24, 48 and 72h of incubation. The cytotoxicities of strychnine and Brucine were found to be time- and concentration-dependent. Strychnine was determined to be more toxic to Vero cells than Brucine. At the same time, the interactions of strychnine and Brucine with DNA were investigated using neutral red (NR) dye as a probe by UV-vis spectroscopy, fluorescence spectroscopy, and an examination of the ionic strength effect, and the effects of alkaloids on DNA melting were also examined.
CONCLUSIONS:
The results indicated that a DNA-Brucine mixture but not a DNA-strychnine mixture could be extracted from Vero cells after treatment with Brucine and strychnine, respectively. Brucine competitively intercalated into the DNA double-helix causing fluorescence quenching of the DNA-NR system. UV absorption spectroscopy and the melting temperature (Tm) curve also provided evidence that Brucine interacted with DNA through intercalation. Furthermore, the results of the ionic strength effect experiment suggested that electrostatic interactions between Brucine and phosphate groups in the DNA backbone might also play an important role in the binding of Brucine to DNA.
| | J Chromatogr A. 2014 Jul 25;1352:1-7. | | Ionic liquid-based electromembrane extraction and its comparison with traditional organic solvent based electromembrane extraction for the determination of strychnine and brucine in human urine.[Pubmed: 24925450] |
METHODS AND RESULTS:
An ionic liquid-based electromembrane extraction (IL-EME) method was presented, and its performance was compared with 2-ethylnitrobenzene (ENB) based EME for the determination of strychnine and brucine in human urine. For the two methods, the fundamental extraction parameters such as supported liquid membrane, voltage, extraction time, pH values of sample solution and acceptor solution, temperature and salting-out effect were separately optimized. IL-EME provided 96- and 122-fold enrichment factors for strychnine and brucine, respectively, which were better than those obtained in EME (83- and 86-fold, respectively). The calibration curves were linear over the ranges of 20-720 μg L(-1) for strychnine and 20-640 μg L(-1) for brucine with the correlation coefficients higher than 0.9950. The repeatability of EME and IL-EME were evaluated by five parallel experiments giving the relative standard deviations of 5.12-6.98%.
CONCLUSIONS:
As the results indicated, 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. |
|
| In vivo: |
| Toxicol Lett. 2013 Oct 24;222(2):91-101. | | Brucine, an alkaloid from seeds of Strychnos nux-vomica Linn., represses hepatocellular carcinoma cell migration and metastasis: the role of hypoxia inducible factor 1 pathway.[Pubmed: 23933019] | Brucine is an alkaloid derived from the seeds of Strychnos nux-vomica Linn. which have long been used as a traditional medicine for the treatment of hepatocellular carcinoma (HCC) in China. HCC prognosis can be greatly influenced by metastasis. There has thus far been little research into Brucine as a source of anti-metastasis activity against HCC.
METHODS AND RESULTS:
In this study, we revealed that Brucine dramatically repressed HepG2 and SMMC-7721 HCC cell migration with few cytotoxic effects. Hypoxia inducible factor 1 (HIF-1) is a key transcription factor mediating cell migration and invasion. Brucine suppressed HIF-1-dependent luciferase activity in HepG2 cells. The transcriptions of four known HIF-1 target genes involved in HCC metastasis, i.e., fibronectin, matrix metallopeptidase 2, lysyl oxidase, and cathepsin D, were also attenuated after Brucine treatment. Experiments in vivo showed that an intraperitoneal injection of 5 and 15 mg/kg of Brucine resulted in dose-dependent decreases in the lung metastasis of H22 ascitic hepatoma cells. Moreover, a dosage of Brucine at 15 mg/kg exhibited very low toxic effects to tumor-bearing mice. Consistently, Brucine downregulated expression levels of HIF-1 responsive genes in vivo.
CONCLUSIONS:
Our current study demonstrated the capacity of Brucine in suppressing HCC cell migration in vitro and lung metastasis in vivo. The inhibition of the HIF-1 pathway is implicated in the anti-metastasis activity of Brucine. |
|
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