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International Journal of Environmental... Aug 2022Anabasine and anatabine are minor alkaloids in tobacco products and are precursors for tobacco-specific nitrosamines (TSNAs). The levels of these two compounds have been...
Anabasine and anatabine are minor alkaloids in tobacco products and are precursors for tobacco-specific nitrosamines (TSNAs). The levels of these two compounds have been used to differentiate tobacco product sources, monitor compliance with smoking cessation programs, and for biomonitoring in TSNA-related studies. The concentrations of urinary anabasine and anatabine were measured in a representative sample of U.S. adults who smoked cigarettes (N = 770) during the 2013−2014 National Health and Nutrition Examination Survey (NHANES) study cycle, which was the first cycle where urinary anabasine and anatabine data became available. Weighted geometric means (GM) and geometric least squares means (LSM) with 95% confidence intervals were calculated for urinary anabasine and anatabine categorized by tobacco-use status [cigarettes per day (CPD) and smoking frequency] and demographic characteristics. Smoking ≥20 CPD was associated with 3.6× higher anabasine GM and 4.8× higher anatabine GM compared with smoking <10 CPD. Compared with non-daily smoking, daily smoking was associated with higher GMs for urinary anabasine (1.41 ng/mL vs. 6.28 ng/mL) and anatabine (1.62 ng/mL vs. 9.24 ng/mL). Urinary anabasine and anatabine concentrations exceeded the 2 ng/mL cut point in 86% and 91% of urine samples from people who smoke (PWS) daily, respectively; in comparison, 100% of them had serum cotinine concentrations greater than the established 10 ng/mL cut point. We compared these minor tobacco alkaloid levels to those of serum cotinine to assess their suitability as indicators of recent tobacco use at established cut points and found that their optimal cut point values would be lower than the established values. This is the first time that anabasine and anatabine are reported for urine collected from a U.S. population-representative sample of NHANES study participants, providing a snapshot of exposure levels for adults who smoked during 2013−2014. The results of this study serve as an initial reference point for future analysis of NHANES cycles, where changes in the national level of urinary anabasine and anatabine can be monitored among people who smoke to show the effect of changes in tobacco policy.
Topics: Adult; Alkaloids; Anabasine; Biomarkers; Cigarette Smoking; Cotinine; Humans; Nicotine; Nutrition Surveys; Pyridines; Nicotiana
PubMed: 35955098
DOI: 10.3390/ijerph19159744 -
Journal of Clinical Medicine Jan 2022Obesity is a leading cause of preventable death in the United States. Currently approved pharmacotherapies for the treatment of obesity are associated with rebound...
Obesity is a leading cause of preventable death in the United States. Currently approved pharmacotherapies for the treatment of obesity are associated with rebound weight gain, negative side effects, and the potential for abuse. There is a need for new treatments with fewer side effects. Minor tobacco alkaloids (MTAs) are potential candidates for novel obesity pharmacotherapies. These alkaloids are structurally related to nicotine, which can help reduce body weight, but without the same addictive potential. The purpose of the current study was to examine the effects of three MTAs (nornicotine, anatabine, and anabasine) and nicotine on weight gain, body composition, chow intake, and physical activity. We hypothesized that the MTAs and nicotine would reduce weight gain through reductions in chow intake and increases in physical activity. To test this, male Sprague Dawley rats were housed in metabolic phenotyping chambers. Following acclimation to these chambers and to (subcutaneous (sc)) injections of saline, animals received daily injections (sc) of nornicotine, anabasine, anatabine, or nicotine for one week. Compared to saline-injected animals that gained body weight and body fat during the treatment phase, injections of nornicotine and anatabine prevented additional weight gain, alongside reductions in body fat. Rats receiving anabasine and nicotine gained body weight at a slower rate relative to rats receiving saline injections, and body fat remained unchanged. All compounds reduced the intake of chow pellets. Nornicotine and nicotine produced consistent increases in physical activity 6 h post-injection, whereas anabasine's and anatabine's effects on physical activity were more transient. These results show that short-term, daily administration of nornicotine, anabasine, and anatabine has positive effects on weight loss, through reductions in body fat and food intake and increases in physical activity. Together, these findings suggest that MTAs are worthy of further investigations as anti-obesity pharmacotherapies.
PubMed: 35159932
DOI: 10.3390/jcm11030481 -
Plants (Basel, Switzerland) Aug 2022The encapsulation of the famous alkaloid, anabasine, with β-CD was studied to obtain a more stable and bioavailable inclusion complex. Various in silico and...
The encapsulation of the famous alkaloid, anabasine, with β-CD was studied to obtain a more stable and bioavailable inclusion complex. Various in silico and experimental studies of the obtained β-CD-anabasine complex are presented. Firstly, molecular docking studies were conducted against the α, β, and γ cyclodextrins to explore which subclass is the best for encapsulation. The obtained results that pointed at β-cyclodextrin were further confirmed by five MD simulations and MM-PBSA studies. Experimentally, the spectral properties of the anabasine β-cyclodextrin complex were determined by FT-IR, H, and C-NMR spectroscopic methods. Additionally, the surface morphology of the anabasine β-cyclodextrin was investigated using a scanning electron microscope. Furthermore, the outputs of the thermographic measurements utilizing a differential scanning calorimeter were displayed. The activation energy of the reaction of thermo-oxidative destruction of the clathrate complex was calculated, and the kinetic parameters of the thermal destruction processes were decided using the Freeman-Carroll, Sharpe-Wentworth, Achar, and Coates-Redfern methods. The kinetic parameters of the thermal decomposition of the anabasine β-cyclodextrin were in agreement and verified the reliability of the obtained results. The obtained computational, spectral, morphological, and thermogravimetric results verified the successful formation of the anabasine β-cyclodextrin complex.
PubMed: 36079665
DOI: 10.3390/plants11172283 -
Molecules (Basel, Switzerland) Oct 2022A series of -acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested...
A series of -acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while the adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity, reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties.
Topics: Animals; Adamantane; Anabasine; Azoles; Pyridines; Analgesics; Anti-Bacterial Agents; Antiviral Agents; Structure-Activity Relationship; Microbial Sensitivity Tests
PubMed: 36364219
DOI: 10.3390/molecules27217387 -
PloS One 2017Floral phytochemicals are ubiquitous in nature, and can function both as antimicrobials and as insecticides. Although many phytochemicals act as toxins and deterrents to...
BACKGROUND
Floral phytochemicals are ubiquitous in nature, and can function both as antimicrobials and as insecticides. Although many phytochemicals act as toxins and deterrents to consumers, the same chemicals may counteract disease and be preferred by infected individuals. The roles of nectar and pollen phytochemicals in pollinator ecology and conservation are complex, with evidence for both toxicity and medicinal effects against parasites. However, it remains unclear how consistent the effects of phytochemicals are across different parasite lineages and environmental conditions, and whether pollinators actively self-medicate with these compounds when infected.
APPROACH
Here, we test effects of the nectar alkaloid anabasine, found in Nicotiana, on infection intensity, dietary preference, and survival and performance of bumble bees (Bombus impatiens). We examined variation in the effects of anabasine on infection with different lineages of the intestinal parasite Crithidia under pollen-fed and pollen-starved conditions.
RESULTS
We found that anabasine did not reduce infection intensity in individual bees infected with any of four Crithidia lineages that were tested in parallel, nor did anabasine reduce infection intensity in microcolonies of queenless workers. In addition, neither anabasine nor its isomer, nicotine, was preferred by infected bees in choice experiments, and infected bees consumed less anabasine than did uninfected bees under no-choice conditions. Furthermore, anabasine exacerbated the negative effects of infection on bee survival and microcolony performance. Anabasine reduced infection in only one experiment, in which bees were deprived of pollen and post-pupal contact with nestmates. In this experiment, anabasine had antiparasitic effects in bees from only two of four colonies, and infected bees exhibited reduced-rather than increased-phytochemical consumption relative to uninfected bees.
CONCLUSIONS
Variation in the effect of anabasine on infection suggests potential modulation of tritrophic interactions by both host genotype and environmental variables. Overall, our results demonstrate that Bombus impatiens prefer diets without nicotine and anabasine, and suggest that the medicinal effects and toxicity of anabasine may be context dependent. Future research should identify the specific environmental and genotypic factors that determine whether nectar phytochemicals have medicinal or deleterious effects on pollinators.
Topics: Anabasine; Animals; Bees; Host-Parasite Interactions; Infections
PubMed: 28832668
DOI: 10.1371/journal.pone.0183729 -
Journal of Psychopharmacology (Oxford,... Oct 2014Nicotine has been well characterized to improve memory and attention. Nicotine is the primary, but not only neuroactive compound in tobacco. Other tobacco constituents...
Nicotine has been well characterized to improve memory and attention. Nicotine is the primary, but not only neuroactive compound in tobacco. Other tobacco constituents such as anabasine and anatabine also have agonist actions on nicotinic receptors. The current study investigated the effects of anabasine and anatabine on memory and attention. Adult female Sprague-Dawley rats were trained on a win-shift spatial working and reference memory task in the 16-arm radial maze or a visual signal detection operant task to test attention. Acute dose-effect functions of anabasine and anatabine over two orders of magnitude were evaluated for both tasks. In the radial-arm maze memory test, anabasine but not anatabine significantly reduced the memory impairment caused by the NMDA antagonist dizocilpine (MK-801). In the signal detection attentional task, anatabine but not anabasine significantly attenuated the attentional impairment caused by dizocilpine. These studies show that non-nicotine nicotinic agonists in tobacco, similar to nicotine, can significantly improve memory and attentional function. Both anabasine and anatabine produced cognitive improvement, but their effectiveness differed with regard to memory and attention. Follow-up studies with anabasine and anatabine are called for to determine their efficacy as therapeutics for memory and attentional dysfunction.
Topics: Alkaloids; Anabasine; Animals; Attention; Conditioning, Operant; Dizocilpine Maleate; Female; Maze Learning; Memory; Nicotinic Agonists; Nootropic Agents; Pyridines; Rats; Smoke; Nicotiana
PubMed: 25122040
DOI: 10.1177/0269881114543721 -
Molecules (Basel, Switzerland) Nov 2023Measurement of multiple nicotine metabolites and total nicotine equivalents (TNE) might be a more reliable strategy for tobacco exposure verification than measuring...
Simultaneous Measurement and Distribution Analysis of Urinary Nicotine, Cotinine, Trans-3'-Hydroxycotinine, Nornicotine, Anabasine, and Total Nicotine Equivalents in a Large Korean Population.
Measurement of multiple nicotine metabolites and total nicotine equivalents (TNE) might be a more reliable strategy for tobacco exposure verification than measuring single urinary cotinine alone. We simultaneously measured nicotine, cotinine, 3-OH cotinine, nornicotine, and anabasine using 19,874 urine samples collected from the Korean National Health and Nutrition Examination Survey. Of all samples, 18.6% were positive for cotinine, 17.4% for nicotine, 17.3% for nornicotine, 17.6% for 3-OH cotinine, and 13.2% for anabasine. Of the cotinine negative samples, less than 0.3% were positive for all nicotine metabolites, but not for anabasine (5.7%). The agreement of the classification of smoking status by cotinine combined with nicotine metabolites was 0.982-0.994 (Cohen's kappa). TNE3 (the molar sum of urinary nicotine, cotinine, and 3-OH cotinine) was most strongly correlated with cotinine compared to the other nicotine metabolites; however, anabasine was less strongly correlated with other biomarkers. Among anabasine-positive samples, 30% were negative for nicotine or its metabolites, and 25% were undetectable. Our study shows that the single measurement of urinary cotinine is simple and has a comparable classification of smoking status to differentiate between current smokers and non-smokers relative to the measurement of multiple nicotine metabolites. However, measurement of multiple nicotine metabolites and TNE3 could be useful for monitoring exposure to low-level or secondhand smoke exposure and for determining individual differences in nicotine metabolism. Geometric or cultural factors should be considered for the differentiation of tobacco use from patients with nicotine replacement therapy by anabasine.
Topics: Humans; Nicotine; Cotinine; Anabasine; Smoking Cessation; Nutrition Surveys; Alkaloids; Tobacco Use Cessation Devices; Biomarkers; Republic of Korea
PubMed: 38067415
DOI: 10.3390/molecules28237685 -
Epigenetics 2022Increasing use of non-combusted forms of nicotine such as e-cigarettes poses important public health questions regarding their specific risks relative to combusted...
Increasing use of non-combusted forms of nicotine such as e-cigarettes poses important public health questions regarding their specific risks relative to combusted tobacco products such as cigarettes. To fully delineate these risks, improved biomarkers that can distinguish between these forms of nicotine use are needed. Prior work has suggested that methylation status at cg05575921 may serve as a specific biomarker of combusted tobacco smoke exposure. We hypothesized combining this epigenetic biomarker with conventional metabolite assays could classify the type of nicotine product consumption. Therefore, we determined DNA methylation and serum cotinine values in samples from 112 smokers, 35 e-cigarette users, 19 smokeless tobacco users, and 269 controls, and performed mass spectroscopy analyses of urine samples from all nicotine users and 22 verified controls to determine urinary levels of putatively nicotine product-specific substances; propylene glycol, 2-cyanoethylmercapturic acid (CEMA), and anabasine. 1) Cigarette smoking was associated with a dose dependent demethylation of cg05575921 and increased urinary CEMA and anabasine levels, 2) e-cigarette use did not demethylate cg05575921, 3) smokeless tobacco use also did not demethylate cg05575921 but was positively associated with anabasine levels 4) CEMA and cg05575921 levels were highly correlated and 5) propylene glycol levels did not reliably distinguish use groups. Cg05575921 assessments distinguish exposure to tobacco smoke from smokeless sources of nicotine including e-cigarettes and smokeless tobacco, neither of which are associated with cg05575921 demethylation. A combination of methylomic and metabolite profiling may allow for accurate classification use status of a variety of nicotine containing products.
Topics: DNA Methylation; Electronic Nicotine Delivery Systems; Nicotine; Nicotiana; Tobacco Products; Vaping
PubMed: 33588690
DOI: 10.1080/15592294.2021.1890875 -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2022The alkaloid-rich fraction obtained by fractionation of the crude methanolic extract of the leaves of wild tobacco tree Graham (Solanaceae) was analyzed using UPLC-MS...
The alkaloid-rich fraction obtained by fractionation of the crude methanolic extract of the leaves of wild tobacco tree Graham (Solanaceae) was analyzed using UPLC-MS and GC-MS. Anabasine, a piperidine alkaloid, was identified as the major constituent with approximately 60 % (/) of the alkaloid-rich fraction. In addition to anabasine, six secondary metabolites were identified using high-resolution UPLC-MS. Anabasine was quantified in the leaves to be 1 mg g dry plant material. The GC-MS analysis revealed five compounds with anabasine as the major component, while nicotine was not detected. Moreover, GC-MS was used for the analysis of the volatile oil that was obtained by hydro-distillation from the leaves of . The volatile plant oil was found to be rich in oxygenated sesquiterpenes (., -bisabolol) and carboxylic acids and esters (., ethyl linoleate and hexadecanoic acid), whereas anabasine was not detected.
Topics: Nicotiana; Gas Chromatography-Mass Spectrometry; Chromatography, Liquid; Tandem Mass Spectrometry; Anabasine; Alkaloids; Plant Leaves
PubMed: 36651530
DOI: 10.2478/acph-2022-0001 -
Journal of Oncology 2022The lung is one of the most common metastatic sites of malignant tumors. Early detection of pulmonary metastatic carcinoma can effectively reduce relative cancer...
BACKGROUND
The lung is one of the most common metastatic sites of malignant tumors. Early detection of pulmonary metastatic carcinoma can effectively reduce relative cancer mortality. Human metabolomics is a qualitative and quantitative study of low-molecular metabolites in the body. By studying the plasm metabolomics of patients with pulmonary metastatic carcinoma or other lung diseases, we can find the difference in plasm levels of low-molecular metabolites among them. These metabolites have the potential to become biomarkers of lung metastases.
METHODS
Patients with pulmonary nodules admitted to our department from February 1, 2019, to May 31, 2019, were collected. According to the postoperative pathological results, they were divided into three groups: pulmonary metastatic carcinoma (PMC), benign pulmonary nodules (BPN), and primary lung cancer (PLC). Moreover, healthy people who underwent physical examination were enrolled as the healthy population group (HPG) during the same period. On the one hand, to study lung metastases screening in healthy people, PMC was compared with HPG. The multivariate statistical analysis method was used to find the significant low-molecular metabolites between the two groups, and their discriminating ability was verified by the ROC curve. On the other hand, from the perspective of differential diagnosis of lung metastases, three groups with different pulmonary lesions (PMC, BPN, and PLC) were compared as a whole, and then the other two groups were compared with PMC, respectively. The main low-molecular metabolites were selected, and their discriminating ability was verified.
RESULTS
In terms of lung metastases screening for healthy people, four significant low-molecular metabolites were found by comparison of PMC and HPG. They were O-arachidonoyl ethanolamine, adrenoyl ethanolamide, tricin 7-diglucuronoside, and p-coumaroyl vitisin A. In terms of the differential diagnosis of pulmonary nodules, the significant low-molecular metabolites selected by the comparison of the three groups as a whole were anabasine, octanoylcarnitine, 2-methoxyestrone, retinol, decanoylcarnitine, calcitroic acid, glycogen, and austalide L. For the comparison of PMC and BPN, L-tyrosine, indoleacrylic acid, and lysoPC (16 : 0) were selected, while L-octanoylcarnitine, retinol, and decanoylcarnitine were selected for the comparison of PMC and PLC. Their AUCs of ROC are all greater than 0.80. It indicates that these substances have a strong ability to differentiate between pulmonary metastatic carcinoma and other pulmonary nodule lesions.
CONCLUSION
Through the research of plasm metabolomics, it is possible to effectively detect the changes in some low-molecular metabolites among primary lung cancer, pulmonary metastatic carcinoma, and benign pulmonary nodule patients and healthy people. These significant metabolites have the potential to be biomarkers for screening and differential diagnosis of lung metastases.
PubMed: 36046366
DOI: 10.1155/2022/9460019