Drug Testing and Analysis
·
2022
·Vol. 15
·期 10
·1099-1106
·
IF 3.234
Shulei Han,Chuan Liu,Huan Chen,Ya'ning Fu,Yuan Zhang,Ruijuan Miao,Peipei Ren,Pengpeng Yu,Zhihao Shi,Yushan Tian,Hongjuan Wang,Tong Liu,Hongwei Hou,Qingyuan Hu
Nicotine lactate, nicotine tartrate, nicotine benzoate, and freebase nicotine (FBN) are four forms of nicotine salt systems that are present in tobacco products. However, few in vivo studies have compared their pharmacological (pK) efficacies, which are important for understanding their roles in the addiction and abuse of tobacco and nicotine products. In this work, the pK of the above nicotine salt systems was studied by subcutaneously injecting their aqueous solutions in rats and obtaining blood samples from the jugular vein. Nicotine levels in the blood were analyzed by LC–MS/MS. The results demonstrated that rapid nicotine absorption occurred in all nicotine systems. Of them, NB had the smallest T max , while FBN had the largest T max . The nicotine metabolic rate and clearance decreased for FBN, indicating that nicotine retention in the body was higher than for the other three salt-based systems. Compared with nicotine salts, FBN could reach and maintain a higher concentration in the animal model. Additionally, as the benzoic acid ratios increased, the C max of the nicotine benzoate (NB) in the plasma decreased. This indicates that the lower the pH, the lower the C max . When different concentrations of NB were used, the higher the NB concentration, the greater the C max and AUC (0-t) . These results demonstrate that nicotine adsorption by NB in the animal model depended on both pH and concentration. This baseline information could be used to explain different clinical pharmacological observations in humans, though this study only considered the effects of nicotine on pharmacokinetics in vivo.
研究领域:
毒理学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2024
·Vol. 16
·期 18
·3048
·
IF 4.8
Zhe Chen,Naiyan Lu,Xu Li,Qingrun Liu,Yujie Li,Xiyue Li,Ximiao Yu,Haotian Zhao,Chang Liu,Xue Tang,Xun Wang,Weisun Huang
Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL/6J mice were subcutaneously injected four times a day with nicotine (2 mg/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg/kg or 0.1 mg/kg), or nicotine (0.1 mg/kg) and caffeine (20 mg/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation.
研究领域:
药理学
·
神经科学
·
行为科学
·
成瘾医学
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DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 12
·期 2
·193-199
·
IF 2.378
Yan-Jun Huang,Qi-Xin Deng,Hong-Qiao Lan,Zheng-Zhong Fang,Hui Chen,Yan Lin,Han-Chun Xu,Tony D. James,Wei Xie
Nicotine exists in e-liquids primarily as the monoprotonated form and free-base form, the former is absorbed by the smoker relatively slowly and the latter is considered the bioavailable form of nicotine. Nowadays e-liquid manufacturers tend to increase nicotine in smoke aerosols, up to a content comparable to conventional cigarettes. Organic acids are added to suppress nicotine in free-base from, because the quick absorption of free-base nicotine (FBN) by the upper respiratory tract produces more bitterness and harshness to smokers. Although several methods have been developed to access FBN in conventional cigarettes or electronic cigarettes, spectrometric methods have rarely been reported. A water-solubility indicator Alizarin Red S (ARS) was introduced for the measurement of free-base nicotine. Since ARS exhibits lower acidity than organic acids, it does not compete for the tertiary amine with organic acids, but can only interact with FBN. The ARS turns from pale yellow to pink once it has been deprotonated by nicotine, and the binding constant between ARS and nicotine was determined to be 1.08 × 106 M−1. A linear calibration curve A = 0.0056c + 0.3309 with r2 = 0.9984 as a function of FBN was constructed, and applied for the evaluation of FBN in prepared e-liquid samples, with RMSE 1.12 mg g−1 for the 20 mg g−1 liquids, and 1.37 mg g−1 for the 50 mg g−1 liquids. The evaluation of FBN in commercial e-liquids agreed well with published e-liquid values. It is believed that the convenient method herein developed will be useful for manufacturers to balance the strength and harshness levels of nicotine in e-liquids.
研究领域:
分析化学
·
毒理学
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产品关联
DOI
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2017
·
IF 3.807
Wenjun Yu,Rongshui Wang,Haiyan Huang,Huijun Xie,Shuning Wang
Agrobacterium tumefaciens S33 can grow with nicotine as the sole source of carbon, nitrogen, and energy via a novel hybrid of the pyridine pathway and the pyrrolidine pathway. Characterization of the enzymes involved in the hybrid pathway is important for understanding its biochemical mechanism. Here, we report that the molybdenum-containing nicotine dehydrogenase (NdhAB), which catalyzes the initial step of nicotine degradation, is located in the periplasm of strain S33, while the 6-hydroxynicotine oxidase and 6-hydroxypseudooxynicoine oxidase are in the cytoplasm. This is consistent with the fact that NdhA has a Tat signal peptide. Interestingly, an open reading frame (ORF) adjacent to the ndhAB gene was verified to encode a copper-containing electron carrier, pseudoazurin (Paz), which has a signal peptide typical of bacterial Paz proteins. Both were transported into the periplasm after being produced in the cytoplasm. We purified NdhAB from the periplasmic fraction of strain S33 and found that with Paz as the physiological electron acceptor, NdhAB catalyzed the hydroxylation of nicotine at a specific rate of 110.52 ± 8.09 μmol · min−1 · mg of protein−1, where the oxygen atom in the hydroxyl group of the product 6-hydroxynicotine was derived from H2O. The apparent Km values for nicotine and Paz were 1.64 ± 0.07 μM and 3.61 ± 0.23 μM, respectively. NAD(P)+, O2, and ferredoxin could not serve as electron acceptors. Disruption of the paz gene disabled the strain for nicotine degradation, indicating that Paz is required for nicotine catabolism in the strain. These findings help our understanding of electron transfer during nicotine degradation in bacteria.IMPORTANCE Nicotine is a toxic and addictive N-heterocyclic aromatic alkaloid produced in tobacco. Its catabolism in organisms and degradation in tobacco wastes have become major concerns for human health and the environment. Bacteria usually decompose nicotine using the classical strategy of hydroxylating the pyridine ring with the help of activated oxygen by nicotine dehydrogenase, which binds one molybdopterin, two [2Fe2S] clusters, and usually one flavin adenine dinucleotide (FAD) as well. However, the physiological electron acceptor for the reaction is still unknown. In this study, we found that the two-component nicotine dehydrogenase from Agrobacterium tumefaciens S33, naturally lacking an FAD-binding domain, is located in the periplasmic space and uses a copper-containing electron carrier, pseudoazurin, as its physiological electron acceptor. We report here the role of pseudoazurin in a reaction catalyzed by a molybdopterin-containing hydroxylase occurring in the periplasmic space. These results provide new biochemical knowledge on microbial degradation of N-heterocyclic aromatic compounds.
研究领域:
微生物学
·
生物化学
·
环境科学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
·
2024
·
IF 0.8
Pan Boyuan,Fu Linna,Du Heng,Liu Guangbin,Duan Bingchao,Lu Kui
RAD51 is a core factor for homologous recombination to repair DNA double-strand breaks and overexpressed in breast cancer cells. Truncated peptide BRC4 (1523-1537) was obtained by computer simulation which had the highest binding free energy targeting RAD51. To enhance the binding affinity to the target protein, six nicotinic acid derivatives were modified at the N -terminal of BRC4 (1523-1537) by Fmoc solid-state synthesis to obtain nicotinamide-modified peptides. The interaction of RAD51 (181-200) with BRC4 (1523-1537) and nicotinamide-modified peptides was verified by circular dichroism (CD) spectroscopy and fluorescence spectroscopy. In conclusion, modifying small molecule pharmacophores can improve binding ability. According to spectral results, 2-chloro-5-fluoronicotinic acid modified BRC4 (1523-1537) has the most significant influence on the secondary structure of RAD51 (181-200); binding constant is 1.1×10 4 L·mol -1 . Cell experiments showed that BRC4 (1523-1537) modified with nicotinic acid N-oxide had the best inhibitory effect on the proliferation of MDA-MB-231 cells.
研究领域:
生物化学
·
癌症研究
·
药物设计
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 16
·4237-4246
·
IF 4.157
Liu Hui,Xia Lei,Shen Chengyin,Huang Chaoqun,Chu Yannan
Methamphetamine (MA) is a highly addictive and illegal psychostimulant drug and is currently one of the most commonly abused illicit drugs in the world. The on-site rapid detection of trace amounts of MA and screening illicit drugs in clandestine laboratories is important for drug enforcement agencies and the forensic community in general. However, detecting methamphetamine in the presence of nicotine and cigarette smoke by ion mobility spectrometry faces difficulty due to the overlapped spectral peaks of methamphetamine and nicotine. In this work, a new method was developed to detect MA using pyridine as a dopant in the presence of nicotine by a homemade ion mobility spectrometry. The reduced mobilities of MA and nicotine were measured under the temperatures of the drift tube from 40 to 120 °C and doping with pyridine. The result shows that the temperature of 100 °C is beneficial to resolve the two substances. The concentration of doped pyridine is optimized to be 18 ppm. In this doped experiment, the reaction rate of nicotine is higher than that of MA by measuring the instrumental responses of MA and nicotine. No matter how high the nicotine content is, the interference of nicotine can be eliminated in the detection of MA doped with pyridine. This method is also successfully applied for the determination of MA and nicotine simultaneously in real saliva samples. The limit of detection of MA was measured to be about 0.5 ng/μL. The promising results in this work provide an effective method for on-site detection of MA. Graphical abstract
研究领域:
分析化学
·
法医学
·
药物检测
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DOI
高影响因子
VIBRATIONAL SPECTROSCOPY
·
2024
·
IF 2.7
Fan Yang,Jing Zhao,Zhengang Wu,Yingna Wei,Hengyong Wei,Jingwu Li,Bo Li
Cocrystal is a new class of pharmaceutical crystal form, which could improve the physical and chemical properties of drug substance without affecting the internal structure of drug substance. Therefore, the cocrystals show a great deal of potential in the development and research of drugs. 5-Fluorouracil (5-FU) is one of the most widely used anti-pyrimidine drugs. However, its solubility is poor and its oral bioavailability is low. In this work, the cocrystal of 5-FU with nicotinamide was prepared by the solvent evaporation method. The cocrystal structure was confirmed by infrared spectroscopy (IR), X-ray diffraction (XRD) and Raman spectroscopy. The X-ray diffraction and infrared spectroscopy presented that there were significantly different peaks between the raw drug and the cocrystal. Raman spectral results also indicated the differences of such cocrystal compared with the raw drug. In addition, TiN-Ag composite SERS substrate was used to study the formation of 5-FU cocrystal drugs and the formation process was dynamically monitored, and the interaction between molecules during the cocrystal reaction was deeply understood. The cocrystal reaction process was tracked, it can be found that the peak intensity of the raw drug and cocrystal changes with the reaction, indicating that the TiN-Ag composite substrate can monitor the cocrystal transformation process.
研究领域:
药学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING RESEARCH & DESIGN
·
2025
·
IF 3.9
Pengfei Lu,Rongcheng Wu,Guangwen Xu,Bin Zhang
The high nicotine content in tobacco extract restricts its application in low-nicotine products. This study presents an economical and efficient methodology for the separation of nicotine using silica gel. The performances of static adsorption, dynamic separation, and regeneration were systematically evaluated. The results indicated that silica gel attained a maximum nicotine adsorption capacity of 73.23 mg/g and reached equilibrium within 30 minutes. Thermodynamic analysis indicated that the process was spontaneous and exothermic. When the water content of silica gel was 20.03 %, its adsorption capacity decreased by approximately 50 %. However, solvent elution and regeneration restored the adsorption capacity to over 95.7 % of that in the anhydrous state. EDS, FTIR, and XPS analyses revealed that the adsorption of nicotine by silica gel mainly depends on hydrogen bonding between surface hydroxyl groups and the pyridine nitrogen of nicotine, with a preferential interaction with the pyridine nitrogen, followed by the pyrrole nitrogen. The nicotine content in the eluted product exceeded 97.79 %, and the recovery rate reached 98.95 % when the silica gel column treatment volume was 6 mL/g. After five reuse cycles, the nicotine recovery rate slightly decreased to 92.15 %. This study provides a scalable and low-cost strategy for efficient nicotine separation, which has significant potential for industrial applications.
研究领域:
烟草科学
·
化学工程
·
分析化学
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产品关联
DOI
高影响因子
Frontiers in Chemistry
·
2024
·
IF 3.8
Xinyan Jin,Decai Meng,Lili Fu,Yang Zhao,Qi Zhang,Zhan Zhang,Xianzhong Yin,Qinpeng Shen,Shuang Wang,Yue Zhang,Le Wang,Ping Lei,Bin Li
Understanding the puff-by-puff delivery mechanisms of key components of heated tobacco products is critical to developing product designs. This study investigates the puff-by-puff release patterns of key components in Natural Smoke Cigarettes (NSCs), which are designed to deliver nicotine without combustion by reducing oxygen content, utilizing a 30-s puff interval, a 2-s puff duration, and a 55 mL puff volume to simulate realistic smoking conditions. By establishing models to analyze the variation of nicotine, glycerol, 1,2-propylene glycol (PG), and water in different functional sections of the cigarette under controlled smoking conditions. These sections include the tobacco, hollow, cooling, and filter sections, constituting the structure of NSCs. In addition, the model calculates the port-by-port release of the components in the flue gas aerosol and compares it with the measured value. The results showed that: The retention amount in the tobacco section showed a steep decline in the first three puffs, with an overall exponential decrease. The amounts in the other sections were consistent, increasing in the first two puffs and then stabilizing. The retention amount decreased linearly with each puff, with a similar pattern across sections. The release amount peaked at the fourth to fifth puffs and then stabilized. The retention amount in the tobacco section declined exponentially in the first three puffs. It peaked in the second to third puffs in other sections, then decreased with each subsequent puff. The retention amount in the tobacco section showed a significant decline in the first puff, stabilizing at around 4 mg. In other sections, it peaked at the first puff and then rapidly declined. These findings can inform the development of reduced-harm smoking products and contribute to a better understanding of the dynamics of smoke generation. Additionally, the study offers a reference for the puff-by-puff release stability of NSCs and the improvement of consumers’ sensory quality.
研究领域:
生物学
·
医学
·
公共卫生
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Zhongnan Huang,Zhenglian Li,Luyao Xu,Chaoguo Wei,Chenting Zhu,Haohua Deng,Huaping Peng,Xinghua Xia,Wei Chen
Monitoring nicotine concentrations in human fluids is extremely crucial owing to the harmful effect of nicotine on human health. Herein, it is shown that nicotine could quench the cathodic electrochemiluminescence (ECL) of gold nanoclusters (AuNCs) with high efficiency. The ECL quenching mechanism of nicotine was studied in detail using various experimental tools and theoretical calculations. It was concluded that the strongly oxidizing intermediate SO4•–, produced from K2S2O8, could oxidized nicotine, resulting in ECL emission quenching. On the basis of this high-efficiency ECL quenching of the AuNCs/K2S2O8 system, a recyclable, ultrasensitive, and selective ECL sensing platform for nicotine detection was proposed. Even in the absence of any complex signal amplification techniques, the ECL sensor for nicotine detection showed an unprecedentedly low detection limit of 7.0 × 10–13 M (S/N = 3) and a wide linear range over 8 orders of magnitude. Most remarkably, it could be successfully used for nicotine detection in human urine samples. This is expected to promote the investigations and applications on nicotine-related diseases. We believe that the proposed ECL platform can hold great prospects for commercialization in biomedical fields and tobacco industries.
研究领域:
分析化学
·
生物医学工程
·
烟草科学
✓ 已验证
DOI
高影响因子
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
·
2024
·
IF 1.3
Yang Qifu,Kun Ma,Ying Liang,Jiaquan Wu,Xinyu Zhang,Yang Shuangyan
Nicotine and glycerol are the two important indexes of reconstituted tobacco and they determine the quality of the reconstituted tobacco. A hand-held near infrared spectrometer was used to collect the spectral data of reconstituted tobacco leaves, and three algorithms of principal component regression, partial least squares and support vector machine were used to build the prediction model of the nicotine and glycerol content in reconstituted tobacco leaves. The experimental results showed that the support vector machine algorithm could achieve the best prediction results compared with principal component regression and partial least squares algorithms. The proposed method can rapidly determine the nicotine and glycerol content of the reconstituted tobacco leaves and it provides a new technical reference for improving the quality of new tobacco.
研究领域:
烟草科学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Xiayu Wu,Yongjun Liu,Changhao Zou,Fuqin He,Fang Guo,Sijia Liu,Yi Fan,Xuedong Zhu,Qianyi Zhou,Dan Shu
Introduction: Traditional Miao and Dai Chinese medicines have used nicotine-rich leaf tobacco to treat traumatic injuries by promoting hemostasis. While nicotine is known to enhance platelet aggregation, its effects on other platelet functions and underlying mechanisms remain unclear.Methods and Results: This study aimed to thoroughly investigate nicotine’s effects on human platelets and its pharmacological mechanisms, using thromboelastography to assess nicotine’s impact on platelet function during coagulation. This study aimed to investigate the functional effects of nicotine on human platelets and elucidate its pharmacological mechanisms. The impact of nicotine on platelet function during the coagulation process was assessed using thromboelastography. Further studies showed that nicotine fully activates washed platelets, promoting aggregation, granule release, adhesion, spreading, and plaque retraction. Concurrently, nicotine was found to enhance the intracellular concentration of calcium ions in platelets ([Ca2+]i). To explore the underlying mechanisms, molecular docking software was employed to identify the platelet membrane receptors PAR1 and PAR4, which exhibited the highest docking scores with nicotine. Intervention with two receptor inhibitors demonstrated that only the PAR4 inhibitor could reverse the stimulatory effects of nicotine on platelet granule release. Through the examination of alterations in the downstream signaling pathways of PAR4 receptors, it was determined that nicotine promo-facilitates the phosphorylation of PI3K, AKT, and ERK1/2 proteins, subsequently contributing to the activation of αIIbβ3 receptors in platelets. Conversely, the application of PAR4 inhibitors was found to reverse these effects.Discussion: In conclusion, nicotine activates αIIbβ3 receptors and significantly enhances platelet function by promoting the phosphorylation of the platelet PAR4 receptor signaling pathway. These findings suggest the potential utility of nicotine as a hemostatic agent.
研究领域:
药理学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）