Brucine

About: Brucine is a research topic. Over the lifetime, 586 publications have been published within this topic receiving 6866 citations. The topic is also known as: 10,11-dimethoxy strychnine.

Brucine induces the apoptosis of U266 multiple myeloma cells by phosphorylation of c-Jun.

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.

Effect of Shodhana (processing) on Kupeelu (Strychnos nux-vomica Linn.) with special reference to strychnine and brucine content.

Abstract: Kupeelu ( Strychnos nux-vomica Linn.) commonly known as nux vomica is a poisonous plant used extensively in various ayurvedic formulations, with great therapeutic significance. Ayurveda recommended the administration of Kupeelu only after purification in different media like cow's urine ( Go mutra ), cow's milk ( Go dugdha ), cow's ghee ( Go ghrita ), Kanji (sour gruel), and so on. Apart from the classical methods some other methods are also adopted by the traditional practitioners using castor oil ( Eranda taila ), ginger juice ( Ardraka swarasa ), in the purification of Kupeelu seeds. In the present study an attempt has been made to purify the seeds by performing two different methods (one classical and another traditional) using Kanji and Ardraka swarasa as Shodhana media. This study reveals that both the methods studied reduce the strychnine and brucine contents in comparison to the raw seeds as determined by high performance thin layer chromatography (HPTLC). After purification in Kanji and Ardraka swarasa, the strychnine content was reduced by 39.25% and 67.82%, respectively, and the brucine content in the purified seeds was also found to have decreased by 17.60% and 40.06%, in comparison to the raw seeds.

Dielectric spectroscopic studies in supercooled liquid and glassy states of Acemetacin, Brucine and Colchicine

Abstract: The physical and chemical instability of amorphous pharmaceuticals during storage has become a major problem for the pharmaceutical industry, as most of the pharmaceuticals including some life saving drugs are also found to be poorly water soluble. Molecular mobility is a key factor to understand the various crucial parameters that determine the stability of amorphous phase. The molecular dynamics in the supercooled liquid and glassy states of three Active Pharmaceutical Ingredients (API) Acemetacin, Brucine and Colchicine were characterized by molecular relaxation (mobility) using broadband dielectric spectroscopy (BDS) in a wide frequency range. Primary structural relaxation and intra-molecular (non Johari-Goldstein) secondary relaxation were observed above and below Tg respectively in all three title compounds. The dielectric spectra were fitted to the Havriliak-Negami (HN) function. The temperature dependence of the structural relaxation time followed Vogel-Fulcher-Tamman (VFT) equation and the secondary relaxation followed Arrhenius equation. By Coupling model (CM) prediction, the secondary relaxations in all title compounds were found to be non JG. The width of the structural relaxation peak decreases with temperature for brucine and colchicine while it increases for acemetacin. By Differential Scanning Calorimetry (DSC) experiment, we confirmed that the selelcted compounds are good glass formers and their structural properties and hydrogen bonding were studied by Fourier Transform Infrared spectroscopy (FTIR) and verified by Density Functional theory (DFT). By BDS, the parameters which describe the molecular dynamics in the supercooled and glassy states of the title compounds, like glass transition temperature (Tg) the width of the α relaxation (βKWW), the temperature dependence of α-relaxation times (τα), the fragility (m) and the activation energy of the secondary relaxation (Ea-γ), were determined. The higher values of Tg determined (307.9 K for acemetacin, 366.2 K for brucine and 374.5 K for colchicine) indicates stability of their amorphous phase at normal storage conditions. The fragility index values of the title compounds indicate intermediately fragile behaviour. The FTIR analysis of the crystalline and amorphous states of brucine, acemetacin and colchicine shows the presence of hydrogen bonding in amorphous phase of the title compounds and verified that their molecular structures were retained in the amorphous state.

Interactions between allosteric modulators and 4-DAMP and other antagonists at muscarinic receptors: potential significance of the distance between the N and carboxyl C atoms in the molecules of antagonists.

Abstract: Allosteric enhancement of the affinity of muscarinic receptors for their ligands offers a new way to influence cholinergic neurotransmission. The structure of the allosteric binding domain(s) and the features of agonists, antagonists and modulators which determine the occurrence of either positive or negative cooperativity require clarification. We tested interactions between allosteric modulators alcuronium, strychnine and brucine and eight antagonists at muscarinic receptors expressed in CHO cells. In experiments with unlabeled antagonists, all three modulators enhanced the affinity for 4-diphenylacetoxy-N-dimethylpiperidinium (4-DAMP) at the M2 receptors, and strychnine did so also at the M4 receptors. Positive interactions were also observed between alcuronium and L-hyoscyamine (M2) and scopolamine (M2), between strychnine and butylscopolamine (M4), L-hyoscyamine (M2 and M4) and scopolamine (M4), and between brucine and scopolamine (M2). Positive effects of alcuronium, strychnine and brucine on the affinity of the M2 receptors for 4-DAMP have been confirmed by direct measurements of the binding of [3H]-4-DAMP. A comparison of molecular models of several antagonists which are esters revealed that antagonists in which the distance between the N and the carboxyl C atoms corresponds to five chemical bonds are more likely to display positive cooperativity with alcuronium at the M2 receptors than the antagonists in which the N-carboxyl C distance corresponds to four chemical bonds.