Showing papers on "Brucine published in 2020"
TL;DR: The physicochemical properties, pharmacological activities, and toxicity of brucine were reviewed, and the novel strategies to address the toxicity issues were discussed, aiming to bring new insights into further research and application of this active component.
Abstract: Brucine, a weak alkaline indole alkaloid, is one of the main bioactive and toxic constituents of Nux-vomica. Modern pharmacology studies and clinical practice demonstrate that brucine possesses wide pharmacological activities, such as anti-tumor, anti-inflammatory, analgesic, and the effects on cardiovascular system and nervous system, etc. However, its central nervous system toxicity severely limits its clinical application. Herein, the physicochemical properties, pharmacological activities, and toxicity of brucine were reviewed, and the novel strategies to address the toxicity issues were discussed, aiming to bring new insights into further research and application of this active component.
47 citations
TL;DR: BNO administration dose-dependently attenuated alcohol consumption without affecting food intake, total fluid consumption or the natural preference for a sucrose solution, with 70 mg/kg BNO reducing consumption by 22.8%.
Abstract: Background Alcohol use disorder places a heavy burden on global public health systems and thus is in urgent need of improved pharmacotherapies. Previously, our group has demonstrated that 30 mg/kg of the indole alkaloid brucine significantly attenuates alcohol-drinking behavior; however, the high toxicity, poor water solubility, short half-life, and limited therapeutic window of brucine restrain its clinical application as an antialcoholism medication. We subsequently hypothesized that the oxide of brucine (brucine N-oxide) would produce a similar behavioral effect without the risk profile associated with brucine. Methods Male Fawn-Hooded rats with high innate alcohol preference underwent 2-bottle choice procedures (Experiments 1 to 3). Experiment 1 examined the effects of 7 daily BNO injections of 0, 30, 50, or 70 mg/kg (s.c.) on voluntary alcohol consumption (n = 9/group). Experiment 2 evaluated the impact of a single dose of 0 or 70 mg/kg BNO on the increased alcohol intake induced by a 4-day alcohol deprivation (n = 8/group). Experiment 3 tested the effect of 7 daily BNO injections of 0 or 70 mg/kg (s.c.) on sucrose preference (n = 6/group). Experiment 4 measured the median lethal dose (LD50) values of BNO and brucine to compare their acute toxicity in rats. Experiment 5 tested whether BNO (0, 30, 50, and 70 mg/kg, s.c.) affected locomotor activity using an open-field paradigm (n = 8/group). Finally, Experiment 6 evaluated the possible conditioned rewarding effects of 0, 30, 50, and 70 mg/kg BNO using the conditioned place preference paradigm (n = 6/group). Results BNO administration dose-dependently attenuated alcohol consumption without affecting food intake, total fluid consumption, or the natural preference for a sucrose solution, with 70 mg/kg BNO reducing consumption by 22.8%. A single dose of 70 mg/kg BNO significantly inhibited the alcohol deprivation effect. The LD50 values of BNO and brucine in rats were determined to be 1,103.5 ± 177.0 mg/kg and 264.6 ± 17.7 mg/kg, respectively. Finally, BNO administration did not affect spontaneous locomotor activity or induce a place preference. Conclusions BNO may help to control excessive alcohol use and should be considered a treatment strategy for future study and development.
8 citations
TL;DR: An electrochemical sensor for HA measurements based on a brucine/SWNTS-modified GC electrode using amperometry that shows a linear relationship toward HA concentration and was used to assay HA in pharmaceuticals including hydroxyurea tablets and pralidoxime iodide injections with satisfactory results.
Abstract: Based on the intrinsic electrochemical features of brucine integrated with carbon nanotubes (brucine/SWNTs), dimeric quinoid brucine was electrochemically generated by electroactivation of a brucine/SWNTs-modified GC electrode and used as a novel electrocatalyst for efficient electro-oxidation of hydroxylamine (HA). The electrocatalytic activity was investigated with cyclic voltammetry in the range pH 2.0 to pH 11.0, and the best electrocatalytic performance of the electrocatalyst was obtained at pH 10.0. By taking advantage of the electrocatalytic activity of the dimeric quinoid brucine toward HA, we have developed an electrochemical sensor for HA measurements based on a brucine/SWNTS-modified GC electrode using amperometry with the applied potential of + 0.1 V (vs. Ag/AgCl). Under the optimized conditions, the current response toward HA concentration shows a linear relationship in the dynamic ranges of 0.1–10 μM and 10–1000 μM with a detection limit of 0.021 μM based on the 3σ criterion. The sensor was used to assay HA in pharmaceuticals including hydroxyurea tablets and pralidoxime iodide injections with satisfactory results. The spike-and-recovery for samples of tap water (n = 9) and lake water (n = 9) was within 97.17–100.16%.
7 citations
TL;DR: The developed method, based on ultrasound-assisted dispersive liquid-liquid microextraction coupled to thin-layer chromatography-image analysis, was successfully applied for the determination of strychnine and brucine in Ayurvedic formulations and blood samples.
Abstract: A simple, rapid, cost-effective and green analytical method is developed based on ultrasound-assisted dispersive liquid-liquid microextraction (US-DLLME) coupled to thin-layer chromatography (TLC)-image analysis for the simultaneous determination of two major alkaloids of Strychnos nux-vomica L i.e., strychnine and brucine. The method is composed of three steps, namely (i) US-DLLME by injecting a mixture of 100-μL chloroform (extraction solvent) and 1-mL methanol (disperser solvent) in 5 mL of aqueous sample, followed by ultrasonication and centrifugation, (ii) TLC of 20 μL of sedimented phase with methanol: ammonia (100:1.5, v/v) as the mobile phase and visualization under ultraviolet radiation (254 nm) and (iii) photography of TLC plate and quantification of spots by image analysis using freely available imageJ software (National Institute of Health, Bethesda, MD, USA). The limit of detection and limit of quantification for both alkaloids were found to be in the range of 0.12-0.15 and 0.36-0.48 μg/spot, respectively. The method was found to be linear in the range of 0.5-5 μg/spot with correlation coefficient (R2) of 0.995 and 0.997 for strychnine and brucine, respectively. The developed method was successfully applied for the determination of strychnine and brucine in Ayurvedic formulations and blood samples. The method does not require any sophisticated instrument and handling skills and can be adopted for rapid analysis of strychnine and brucine in forensic toxicological laboratories.
4 citations
DOI•
01 Aug 2020TL;DR: The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression, which is affected by P-glycoprotein expression in the Caco-2 cell line.
Abstract: Objective To investigate the antagonistic effect of the extract of Baizhu (Rhizoma Atractylodis Macrocephalae) (RAM) on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica (NUX) and propose the mechanism of these effects. Methods The apparent permeability value (Papp) and absorption rate constant (Ka) were chosen as indices. The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine. To confirm the results, the brucine and strychnine concentrations in hepatic portal venous blood were determined. Western blotting was used to study P-glycoprotein (P-gp) expression in the Caco-2 cell line. Results Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor, but no significant increase was noted in the presence of a tight junction regulator. The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression. Conclusion The primary absorption mechanism for brucine and strychnine is passive transport, which is affected by P-gp.
3 citations
Journal Article•
TL;DR: In this article, the effects of licorice water extracts (LWE) on the pharmacokinetics of brucine were evaluated in the presence of LWE in rats.
Abstract: The detoxification effects of licorice are believed to be related to its pharmacokinetic (PK) interference. This paper aimed to evaluate the effects of licorice water extracts (LWE) on the pharmacokinetics of brucine. Rats were administered brucine and/or LWE. The pharmacokinetic behavior of brucine and bioactive components of licorice were quantified by HPLC-MS/MS. P-glycoprotein (P-gp) inhibitor verapamil, real time PCR, vesicular transport assay and everted gut sacs were employed to investigate its possible mechanism. We found LWE reduced the Cmax and AUC of oral brucine in a dose-dependent way. In contrast, the AUC values of intraperitoneal brucine showed no significant difference between LWE treated and untreated rats, which indicating the intestinal absorption of brucine was influenced by LWE. We found that high dose of LWE activated the transport activity of P-gp in vesicular transport assay, while the mRNA level of P-gp in the intestinal was not affected by licorice. Moreover, high dose of LWE decreased the intestinal absorption of brucine in the everted gut sacs model, which could over turned by verapamil. These results suggested that a single high dose of LWE could impair the intestine absorption of brucine, and its potential mechanism may be mediated by P-gp in intestine.
Patent•
20 Feb 2020
TL;DR: In this article, a method for preparing an extract of Strychnos nux-vomica, the method comprising: (1) soaking Stryhnos Nux-Vomica with a first alkaline solution, followed by performing solid-liquid separation to obtain a solid matter; (2) extracting the solid matter obtained in step (1), with ethyl acetate, then applying the extraction solution to silica gel column chromatography to obtain an eluate, the eluent being an absolute ethanol or an ethanol solution added with at least one of
Abstract: The present invention belongs to the field of medicine and relates to a method for preparing an extract of Strychnos nux-vomica, the method comprising: (1) soaking Strychnos nux-vomica with a first alkaline solution, followed by performing solid-liquid separation to obtain a solid matter; (2) extracting the solid matter obtained in step (1) with ethyl acetate, followed by performing solid-liquid separation to obtain an extraction solution (3) subjecting the extraction solution obtained in step (2) to silica gel column chromatography to obtain an eluate, the eluent being an absolute ethanol or an ethanol solution added with at least one of an ammonia solution, a potassium carbonate solution, a sodium carbonate solution, a sodium bicarbonate solution and potassium bicarbonate solution; (4) drying the eluate to obtain a dried matter; (5) dissolving the dried matter in an acid solution, followed by performing solid-liquid separation to obtain a liquid matter; (6) adjusting the pH value of the liquid matter obtained in step (5) to 8-13, followed by performing solid-liquid separation to obtain a solid matter; and (7) subjecting the solid matter obtained in step (6) to recrystallization. The present invention relates to the extract of Strychnos nux-vomica and a medical use thereof. The extract of Strychnos nux-vomica of the present invention has a high content of brucine and a low content of strychnine, and is safe and effective for use.
Patent•
20 Mar 2020
TL;DR: In this paper, a double-step nux vomica processed product extract is described. But the active ingredients of the double step nux vomitica processed extract are alkaloids generated by reaction of strychnine and brucine with phenolic or weakly acidic components in ginger, and conditions for the development of the dosage form of the processed product are created.
Abstract: The invention provides a double-step nux vomica processed product extract The active ingredients of the double-step nux vomica processed product extract are alkaloids generated by reaction of strychnine and brucine with phenolic or weakly acidic components in ginger By the double-step nux vomica processed product extract provided by the invention, the defect that a small amount of strychnine andbrucine are retained in the nux vomica extract is overcome, the size is reduced, and conditions for the development of the dosage form of the nux vomica processed product are created