Minor Alkaloids Research Articles

Intraspecific Variation in the Alkaloids of Adalia decempunctata (Coleoptera, Coccinellidae): Sex, Reproduction and Colour Pattern Polymorphism

In this paper, we examine intraspecific variation in the quantity of alkaloid chemical defence in field collected individuals of the polymorphic ladybird beetle Adalia decempunctata (10-spot ladybird). Like its more widely studied relative Adalia bipunctata (2-spot ladybird), A. decempunctata possesses the alkaloids adaline and adalinine, which are, respectively, the major and minor alkaloids of A. bipunctata. We focused especially on alkaloid concentration in relation to colour pattern morph, sex, and the relationship between female and egg parameters. There was a marked sexual dimorphism in the balance of the two alkaloids, with adaline predominating in females and adalinine predominating in males: in males, on average, over 70% of total alkaloid was adalinine. Females had a lower proportion of adalinine (< 10%) than their eggs (> 15%) and relationships between egg alkaloid and female alkaloid or fecundity were weak or non-existent. Colour pattern morph had a borderline (although not) significant relationship with adaline concentration and total alkaloid concentration, which could be further explored with laboratory reared individuals. The sexual dimorphism in alkaloid content, which seems likely due to differences in synthesis, might be related to their relative costs to the two sexes and might provide insight into the evolution of alkaloid diversity in ladybirds.

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination.

β-Nicotyrine (β-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. β-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine β-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm. The pharmacodynamics of β-Nic were examined in vitro, and a nicotine discrimination paradigm was used to determine if β-Nic (0 - 5.0 mg/kg) shares discriminative stimulus properties with Nic (0.2 mg/kg) in male (n = 13) and female (n = 14) rats after 10- & 60-min β-Nic pretreatment delays. A second group of rats was trained to discriminate β-Nic and Nornicotine (Nornic) from saline to determine if β-Nic alone has interoceptive properties and whether they are similar to Nornic. β-Nic had similar binding affinity and efficacy at the α4β2 nicotinic receptor subtype as Nornic, ~50% of Nic efficacy. However, β-Nic only weakly substituted for Nic during substitution testing in female rats, but not males, whereas Nornic fully substituted for Nic. Combination testing at the 10 and 60-min pretreatment intervals showed that β-Nic dose-dependently increased the duration of nicotine's discriminative stimulus effects, especially at the 60-min delay. Drug naïve rats could reliably discriminate Nornic, but not β-Nic, from Sal. β-Nic increased and prolonged the interoceptive stimulus properties of Nic, suggesting it may alter to the abuse liability of ENDS through its ability to slow Nic metabolism.

Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats.

Kratom and cannabidiol products are used to self-treat a variety of conditions, including anxiety and pain, and to elevate mood. Research into the individual pharmacokinetic properties of commercially available kratom and cannabidiol products has been performed, but there are no studies on coadministration of these products. Surveys of individuals with kratom use history indicate that cannabidiol use is one of the strongest predictors of both lifetime and past month kratom use. The purpose of this study was to determine if there are changes in pharmacokinetic properties when commercially available kratom and cannabidiol products are administered concomitantly. It was found that with concomitant administration of cannabidiol, there was a 2.8-fold increase in the exposure of the most abundant kratom alkaloid, mitragynine, and increases in the exposure of other minor alkaloids. The results of this work suggest that with cannabidiol coadministration, the effects of kratom may be both delayed and increased due to a delay in time to reach maximum plasma concentration and higher systemic exposure of the psychoactive alkaloids found in kratom.

The influences of alkaloids of Chelidonium majus L., Colchicum autumnale L, Catharanthus roseus (L.) G.Don and Vinca minor L. on malignant neoplasms, the review of modern researches.

natural alkaloids of Chelidonium majus L., Colchicum autumnale L. and Catharanthus&#x0D; roseus (L.) G.Don are anticancer agents. Some of them, such as colchicine, vincristine and vinblas-tine, are used in modern medicine, as chemotherapy medicines against malignant neoplasms, some of&#x0D; them are effective supplement to conventional methods or works to prevent cancer onset (chelidonine,&#x0D; sanguinarine, chelerythrine, protopine and allocryptopine). The effect of mitotic poisons that are al-kaloids of Colchicum autumnale colchicine, Catharanthus roseus vincristine and vinblastine against&#x0D; malignant neoplasms began to be studied in the last century, the fact of mitotic spindle violation is giv-en in a large number of works. However, the mechanisms of apoptosis under their influence have been&#x0D; little studied. The alkaloids of Chelidonium majus and Vinca minor L. have been much less studied,&#x0D; both in clinical studies and experimental ones, including insufficiently researched their anti-prolifera-tive action, the ability to cause apoptosis and its possible mechanism. The research of apoptosis mech-anisms caused by natural antitumor agents, will allow creating more effective and saving medicines&#x0D; based on the active ingredients of plant raw materials in the future. The aim of the paper was the anal-ysis of the effect of the main alkaloids of Chelidonium majus, Colchicum autumnale, Catharanthus&#x0D; roseus and Vinca minor on malignant neoplasms and the mechanisms of such an influence with thehelp of analytic review of foreign and Ukrainian literature for the period 2002-2023 using medicaldatabase PubMed. The researched data obtained on cell lines, laboratory animals (in vitro) and clinicstudies were analyzed. According to the analysis of the literature of recent years, the cytotoxic and&#x0D; anti-proliferative effects of natural alkaloids of Chelidonium majus chelidonine, Colchicum autum-nale colchicine, Catharanthus roseus vincristine and vinblastine and Vinca minor vincamine on ma-lignant neoplasms can be considered proven. Colchicine caused apoptosis in high doses, chelidonine,&#x0D; on the contrary, caused apoptosis of malignant cells in relatively low doses; in large doses it causedautophagy. The signaling pathways of apoptosis mechanisms of malignant cells under the influenceof chelidonine, colchicine, vincristine, vinblastine and vincamine are much less studied and requireadditional research. Most of the results support the mitochondrial pathway, but there is a view in favorof the receptor-mediated pathway. The medicine, which contained alkaloids of Chelidonium majus, showed a positive effect when used in combination with conventional antitumor therapy. Chelidoniummajus and Vinca minor alkaloids are candidates for their use in antitumor therapy, but clinical studiesof these agents are insufficient.

Minor alkaloids from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla

Seven new monoterpene alkaloids (1 − 7), along with 16 known analogues, were isolated from an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). Their structures were determined by spectroscopic data analysis, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are stereoisomers belonging to a novel type of pseudoindoxyl monoterpene alkaloids, 3 is the first monoterpene furoindole alkaloid from nature, and 4 − 7 are derivatives of the known monoterpene alkaloids featuring different structures.

Effect of combining tobacco cultivars of different alkaloid contents on the development of Lasioderma serricorne (F.) (Coleoptera Anobiidae)

The cigarette beetle, Lasioderma serricorne (F.) (Coleoptera: Anobiidae) is a universal feeder of stored tobacco, resulting in significant economic losses to tobacco manufacturing. Interestingly, few insects can and will infest tobacco due in part to nicotine toxicity. However, the cigarette beetle (CB) presumably metabolizes or secretes with little or no degradation the ingested nicotine allowing for the proliferation of CB progeny to infest stored tobacco. Although the effects of nicotine as an alkaloid have been characterized in the CB, it is not fully understood, nor are the effects of other alkaloids such as nornicotine, anabasine and anatabine with respect to a low nicotine level on the CB. Here we determine the influence of tobacco alkaloid content on population growth of the CB in the laboratory when fed on blends of different tobacco lines (TLA, TLB and TLG) that contained different concentrations of nicotine and three other minor alkaloids. Despite TLA and TLB had lower total alkaloid content than TLG (0.2, 1.1, and 3.5%, respectively), progeny production of CB was delayed only in TLB, suggesting that CB progeny suppression may not be, at least directly, dependent of nicotine content but positively correlated with increases in anatabine. Temperatures of 25° to 30 °C of stored tobacco resulted in severe infestations in mixtures of tobacco suitable for development. These findings indicate the potential to regulate insect infestation via alkaloid content utilizing low nicotine levels.

Examining the Psychoactive Differences between Kratom Strains.

Kratom (Mitragyna speciosa) is a Southeast Asian plant containing various alkaloids that induce pharmacological effects in humans. In Western countries, online vendors sell a variety of different kratom strains which are marketed to have distinct effect profiles. However, as of yet such marketing claims are unsubstantiated, and therefore the current study investigated whether differently colored kratom products can induce distinct effects, as self-reported by users. Six hundred forty-four current kratom users were anonymously surveyed to compare the self-reported effects of and motivations for using kratom products sold as red, green, and white strains. Most of the survey respondents were customers of the same kratom vendor, the products of which had been analyzed for their alkaloid content by an independent laboratory. The survey respondents reported distinct subjective experiences for different kratom strains, in a manner congruent with common marketing descriptions. However, the product analyses revealed no significant cross-strain differences in alkaloid content, suggesting that the reported effect differences might be disproportionally influenced by marketing narratives and anecdotal reports. Future studies should engage a more diverse population and include kratom strains from various vendors. Controlled, blinded experiments could assess whether the reported effect differences stem from a placebo effect or from alternative factors, e.g., minor alkaloids and terpenes.

Bio-evaluation of Untapped Alkaloids from Vinca minor Enriched by Methyl-jasmonate-induced Stress: an Integrated Approach.

The low amount of metabolites isolated from natural products is one of the challenges preventing their biological evaluation. The modulation of biosynthetic pathways by stimulating stress-induced responses in plants was proven to be a valuable tool for diversification of already known natural products. Recently, we reported the dramatic effect of methyl jasmonate (MeJA) on Vinca minor alkaloids distribution. In this study, three compounds identified as 9-methoxyvincamine, minovincinine, and minovincine are successfully isolated in good yield and subjected to several bioassays based on a network pharmacology study. The extracts and isolated compounds show weak to moderate antimicrobial and cytotoxic activities. Also, they are found to significantly promote wound healing in scratch assay, and transforming growth factor-β (TGF-β) modulation is suggested to be the potential pathway based on bioinformatic analysis. Hence, Western blotting is used to assess the expression of several markers related to this pathway and wound healing. The extracts and isolated compounds are able to increase the expression of Smad3 and Phosphatidylinositol-3-kinase (PI3K), while downregulating the levels of cyclin D1 and the mammalian target of rapamycin (mTOR) except for minovincine, which increases the mTOR expression, inferring that it might act through a different mechanism. Molecular docking is used to give insights on the ability of isolated compounds to bind with different active sites in mTOR. Collectively, the integrated phytochemical, in silico, and molecular biology approach reveal that V.minor and its metabolite could be repurposed for the management of dermatological disorders where these markers are dysregulated, which opens the gate to develop new therapeutics in the future.

The analysis of cannabinoids in e-cigarette liquids using LC-HRAM-MS and LC-UV

The use of cannabidiol or CBD products has skyrocketed in the last five years due to the alleged therapeutic benefits, a low potential for abuse and lack of the typical psychoactive effects associated with the use of cannabis products containing high levels of ∆9-tetrahydrocannabinol (∆9-THC). In Belgium, CBD-containing e-liquids with a total THC content lower than 0.2% (w/w) are currently legal. In order to verify the compliance of the different CBD-containing e-cigarette liquids that are available to the Belgian population, a method was developed for screening of 17 cannabinoids and to quantify the major cannabinoids such as CBD, CBDA, ∆9-THC and ∆9-THCA. The latter was fully validated using the ‘total error’ approach, applying accuracy profiles and conforming to ISO17025. None of the analysed samples exceeded the legal limit for the total amount of ∆9-THC present. However, of the 20 CBD-liquids investigated in this study, only 30% of the samples contained an amount of CBD that was within 10% deviation of the label claim. Moreover, the CBD e-liquids labelled “full/broad spectrum” consisted of several minor alkaloids in comparison to the “classic” CBD e-liquids where the acidic forms of the cannabinoids were not present. Currently, no legislation is available for the regulation of CBD e-liquids, however these results indicate that quality controls are pertinent especially concerning the discrepancy in CBD label accuracy.

Determination of the Total Alkaloid Content of Thermopsis Dry Extract by HPTLC - Densitometry

When used to quantify alkaloids in thermopsis dry extract, acidimetric titration has several limitations, including insufficient specificity of the method and arbitrary selection of a titration endpoint. Different parts of the Thermopsis lanceolata plant produce alkaloids in different proportions: the herb is rich in thermopsine, whereas the seeds are rich in cytisine. Since thermopsine and cytisine have different pharmacological effects, it is important to identify and quantify individual alkaloids in thermopsis dry extract.The aim of the study was to develop and validate an analytical procedure for identifying and quantifying total alkaloids in thermopsis dry extract by high-performance thin-layer chromatography (HPTLC) with densitometric detection.Materials and methods. The study included samples from two pilot-scale batches of thermopsis dry extract and reference standards for cytisine and thermopsine. The authors used Merck HPTLС Silica Gel 60 F254 20×10 cm plates for chromatographic separation and analysed the results with a CAMAG® TLC Scanner 4 densitometer and the winCATS software.Results. The authors identified thermopsis dry extract using HPTLC separation followed by spectrodensitometry. The alkaloid-specific solution applied to chromatography plates helped to identify the three most abundant and four minor alkaloids of thermopsis. The most abundant alkaloids were thermopsine, cytisine, and an unidentified alkaloid with a retention factor of approximately 0.2. These three alkaloids accounted for almost 80% of the total alkaloid content of the dry extract. The authors quantified cytisine, thermopsine, and total alkaloids expressed as thermopsine.Conclusions. The authors developed and validated an analytical procedure for identifying and quantifying total alkaloids in thermopsis dry extract. This procedure offers the possibility of reducing the analysis time from 4–5 hours to 2–2.5 hours.

Non-nicotine constituents in cigarette smoke extract enhance nicotine addiction through monoamine oxidase A inhibition.

Tobacco addiction has been largely attributed to nicotine, a component in tobacco leaves and smoke. However, extensive evidence suggests that some non-nicotine components of smoke should not be overlooked when considering tobacco dependence. Yet, their individual effect and synergistic effect on nicotine reinforcement remain poorly understood. The study herein focused on the role of non-nicotine constituents in promoting the effects of nicotine and their independent reinforcing effects. Denicotinized cigarettes were prepared by chemical extracting of cut tobacco, and the cigarette smoke extracts (CSE, used as a proxy for non-nicotine ingredients) were obtained by machine-smoking the cigarettes and DMSO extraction. The compositions of harmful components, nicotine, and other minor alkaloids in both cut tobacco and the CSE of experimental denicotinized cigarettes were examined by GC-MS, and compared with 3R4F reference cigarettes. individually and in synergy with nicotine were determined by conditioned place preference (CPP), dopamine (DA) level detection, the open field test (OFT), and the elevated plus maze (EPM). Finally, the potential enhancement mechanism of non-nicotinic constituents was investigated by nicotine metabolism and monoamine oxidase A (MAOA) activity inhibition in the striatum of mice and human recombinant MAOA. Thenicotine content in smoke from the experimental denicotinized cigarettes (under ISO machine-smoking conditions) was reduced by 95.1% and retained most minor alkaloids, relative to the 3R4F reference cigarettes. It was found that non-nicotine constituents increased acute locomotor activities. This was especially pronounced for DA levels in NAc and CPP scores, decreased the time in center zone. There were no differences in these metrics with DNC group when compared to the NS group. Non-nicotine constituents alone did not show reinforcing effects in CPP or striatum DA levels in mice. However, in the presence of nicotine, non-nicotine constituents further increased the reinforcing effects. Furthermore, non-nicotine constituents may enhance nicotine's reinforcing effects by inhibiting striatum MAOA activity rather than affecting nicotine metabolism or total striatum DA content in mice. These findings expand our knowledge of the effect on smoking reinforcement of non-nicotine constituents found in tobacco products.

Anabasine and Anatabine Exposure Attributable to Cigarette Smoking: National Health and Nutrition Examination Survey (NHANES) 2013-2014.

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.

A comparison of nicotine content methods to produce a UPC2-MS2 method for the analysis of nicotine and minor alkaloids in SPECTRUM nicotine research cigarettes.

Nicotine is the principal alkaloid in tobacco and has been the primary subject of scientific investigation for its pharmacological effects contributing to tobacco use, dependence, withdrawal, and physical harm. Related minor alkaloids, accounting for less than 6% of alkaloid content in tobacco leaves, may also mirror some of the same pharmacological effects. To detect such low concentrations of the minor alkaloids, tobacco product methods produced by the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) using gas chromatography and flame ionization detection (GC-FID) have been adapted for use with gas chromatography-mass spectrometry (GC-MS). Nicotine and minor alkaloid content in SPECTRUM Nicotine Research Cigarettes (NRC) have previously been determined using GC-FID; however, the minor alkaloids were unable to be detected or quantitated. This study employed UltraPerformance Convergence Chromatography (UPC2) system coupled with tandem mass spectrometry (MS2) to determine the nicotine and minor alkaloid content in NRC tobacco products. CORESTA Recommended Methods (CRMs) were adapted for their sample preparative procedures for optimal extraction followed by detection with UPC2-MS2. These results were compared to two separate CRMs that used GC-FID and GC-MS2 as well as an alternative method with GC-MS2 detection. The GC-FID and GC-MS2 CRM preparations along with the alternative GC-MS2 were unable to detect the analytes in every NRC formulation, whereas the UPC2-MS2 extraction and detection method was able to quantify every analyte in every NRC formulation. This increased sensitivity demonstrates the utility of the UPC2-MS2 analytical method in accurately detecting and quantifying nicotine and minor alkaloids in tobacco filler.

Exploration by molecular networking of Strychnos alkaloids reveals the unexpected occurrence of strychnine in seven Strychnos species

IntroductionPlants of the Strychnos genus, which include about 200 species, are used for multiple traditional purposes as hunting poison, for example, and have shown interesting pharmacological properties, especially curarizing and tetanizing, but also against malaria. Many monoterpene indole alkaloids have already been isolated and identified. Among them, there is strychnine, a famous alkaloid that can cause death by asphyxiation. ObjectiveInvestigate alkaloidic molecular diversity from Strychnos genus using molecular networking technique and study the Strychnos genus from a chemotaxonomic point of view. Material and methodsTwenty-eight different species and different plant parts were ground into powder using a grinder. The methanolic extracts were carried out using a pressurized solvent extraction and the alkaloid extract was performed manually with a separating funnel. The extracts were analyzed by HPLC-ESI(+)-Q/TOF. The data were processed using MZmine 2 software and the molecular network was generated on the GNPS platform. The study of the generated molecular network allowed the detection of various alkaloids. Among these is the famous strychnine which has been detected in 7 new Strychnos species not yet described as strychnine producers. This identification was investigated using orthogonal approaches, namely TLC, NMR, HPLC-UV and UHPLC-ESI(+)-Q/TOF analyses. The LOD by HPLC-UV of strychnine was also determined. ResultsFurther analyses allowed to confirm the presence of strychnine in S. densiflora trunk barks but also to show the presence of strychnine with high probability in the trunk barks of S. camptoneura, S. congolana, S. boonei, and S. tchibangensis, and in the leaves of S. usambarensis. About the trunk barks of S. tricalyisoides, the probability of a strychnine content remains low. ConclusionThis work exemplified the efficiency of molecular networking in identifying known metabolites (major and minor alkaloids) involved in the chemotaxonomic study of plants from Strychnos genus.

Kratom (Mitragyna speciosa) Validation: Quantitative Analysis of Indole and Oxindole Alkaloids Reveals Chemotypes of Plants and Products.

Many consumers are turning to kratom ( Mitragyna speciosa ) to self-manage pain and opioid addiction. In the United States, an array of capsules, powders, and loose-leaf kratom products are readily available. Additionally, several online sites supply live kratom plants. A prerequisite to establishing quality control and quality assurance standards for the kratom industry, or understanding how alkaloid levels effect clinical outcomes, is the identification and quantitation of major and minor alkaloid constituents within available products and preparations. To this end, an ultra-high performance liquid chromatography-high resolution mass spectrometry method was developed for the analysis of 8 indole alkaloids (7-hydroxymitragynine, ajmalicine, paynantheine, mitragynine, speciogynine, isopaynantheine, speciociliatine, and mitraciliatine) and 6 oxindole alkaloids (isomitraphylline, isospeciofoleine, speciofoline, corynoxine A, corynoxeine, and rhynchophylline) in US-grown kratom plants and commercial products. These commercial products shared a qualitatively similar alkaloid profile, with 12 – 13 detected alkaloids and high levels of the indole alkaloid mitragynine (13.9 ± 1.1 – 270 ± 24 mg/g). The levels of the other major alkaloids (paynantheine, speciociliatine, speciogynine, mitraciliatine, and isopaynantheine) and the minor alkaloids varied in concentration from product to product. The alkaloid profile of US-grown M. speciosa “Rifat” showed high levels of the indole alkaloid speciogynine (7.94 ± 0.83 – 11.55 ± 0.18 mg/g) and quantifiable levels of isomitraphylline (0.943 ± 0.033 – 1.47 ± 0.18 mg/g). Notably, the alkaloid profile of a US-grown M. speciosa seedling was comparable to the commercial products with a high level of mitragynine (15.01 ± 0.20 mg/g). This work suggests that there are several M. speciosa chemotypes.

Influence of Nitrite on Formation of Tobacco-Specific Nitrosamines in Electronic Cigarette Liquids and Aerosols.

Tobacco-specific nitrosamine (TSNA) formation occurred during aerosol generation from select commercial cig-a-like e-cigarette products. To understand the drivers behind the potential formation of TSNAs in electronic cigarette (e-cigarette) aerosols and e-liquids, model e-liquid systems were generated in the lab to demonstrate that nitrite can react with nicotine and minor alkaloids to form TSNAs in e-liquids. In the presence of nitrite and nicotine, TSNA levels in e-liquids increased over time and the process was accelerated by elevated temperature. Additionally, TSNAs formed during aerosol generation when nitrite was present in the corresponding e-liquids. The commercial e-cigarette products that showed higher levels and formation of TSNAs were observed to contain nitrite and minor alkaloid impurities in the corresponding e-liquids. This study provides valuable information about drivers for TSNA formation in e-liquids and e-cigarette aerosols that may be applied to the evaluation and quality assurance of e-cigarette products.

Isolation and Characterisation of Some Amaryllidaceae Alkaloids from Daffodils Extract Using GCMS Techniques

Haemanthamine an amaryllidaceae alkaloid has growth inhibitory activities against tumour cells such as Rauscher viral leukaemia. It has also been reported to possessed many interesting biological properties including protein synthesis inhibition, anti-parasitic, anti-retroviral activity and cytotoxicity agent against various cancer cells, anti-inflammatory activities and analgesic property. Daffodil is one of the specie in the family Amaryllidaceae, it is commonly called Narcissus in English. In recent years, a lot of technological advances have been deployed in the quest for the discovery of natural products. Most of which majorly favours constituents present in high concentrations and negating those in low concentrations. Thus, this research employed GC-MS techniques being among the most reliable and efficient analytical tools for the evaluation and characterisation of haemanthamine and other minor alkaloids. The results revealed that a total of 12 alkaloids tentatively isolated and characterised by GC-MS.

MEMBRANE TECHNOLOGY IN THE EXTRACTION OF INDOLE ALKALOIDS

By using ultrafiltration membrane with a certain porosity, it is possible to achieve selective fractionation of dimeric and monomeric alkaloids at the molecular weight level. With porosity of the membrane 100-150A° and filtration of alcohol extracts of Vinca rosea L. obtained from the aerial part of the plant, selective fractionation was achieved within the molecular masses from M+ 168 to M+ 426. In the fraction of minor alkaloids, a norharman (M+ 168), dihydrositsirikin (M+ 356) and vindorosine (M+ 426) were identified by the method of LC-MS/MS and GC/MS. The fraction of the minor alkaloids showed strong cytotoxic activity against the DLD-1 and WS-1 cell lines (Resazurin test), and according to the Hoechst test, to the cells of all A-549, DLD-1 and WS-1 lines.

Antiplasmodial activity of constituents and their metabolites after in vitro gastrointestinal biotransformation of a Nauclea pobeguinii extract

Nauclea pobeguinii is traditionally used for treatment of malaria. Previous studies on the plant extract and strictosamide, the putative active constituent, showed a profound in vivo activity of the extract but no in vitro activity of strictosamide. This might indicate that one or more compounds present in the extract, most likely alkaloids, act as prodrugs undergoing biotransformation after oral administration resulting in the active compounds. The phytochemical composition of a N. pobeguinii extract was characterized using UHPLC-UV-HRMS (Ultrahigh-Performance Liquid Chromatography-Ultraviolet-High Resolution Mass Spectrometry) data. An in vitro gastrointestinal model was used to simulate biotransformation of the extract allowing monitoring of the relative abundances of individual constituents over time on one hand, while antiplasmodial activity and cytotoxicity of the biotransformed extract could be evaluated on the other hand. A diversity of compounds was (tentatively) identified in the extract, mainly saponins and alkaloids, including 32 compounds that have not been reported before in N. pobeguinii. The automated data analysis workflow used for unbiased screening for metabolites showed that glycosylated compounds decreased in intensity over time. Alkaloids containing no sugar moieties, including angustine-type alkaloids, showed no gastrointestinal biotransformation. In vitro gastrointestinal biotransformation of strictosamide did not result in a major metabolite. Moreover, multivariate data analysis using Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA) showed no in vitro activity of strictosamide or its metabolites suggesting that other compounds or metabolites present in the extract are responsible for the antiplasmodial effect of the N. pobeguinii extract. The OPLS-DA proposes alkaloids with a β-carboline moiety as active principles, suggesting that antiplasmodial activity of N. pobeguinii derives from an additive or synergistic effect of multiple minor alkaloids and their metabolites present in the bark extract of N. pobeguinii.

Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions.

Tobacco use disorder continues to be a leading public health issue and cause of premature death in the United States. Nicotine is considered as the major tobacco alkaloid causing addiction through its actions on nicotinic acetylcholine receptors (nAChRs). Current pharmacotherapies targeting nicotine’s effects produce only modest effectiveness in promoting cessation, highlighting the critical need for a better understanding of mechanisms of nicotine addiction to inform future treatments. There is growing interest in identifying potential contributions of non-nicotine components to tobacco reinforcement. Cotinine is a minor alkaloid, but the major metabolite of nicotine that can act as a weak agonist of nAChRs. Accumulating evidence indicates that cotinine produces diverse effects and may contribute to effects of nicotine. In this review, we summarize findings implicating cotinine as a neuroactive metabolite of nicotine and discuss available evidence regarding potential mechanisms underlying its effects. Preclinical findings reveal that cotinine crosses the blood brain barrier and interacts with both nAChRs and non-nAChRs in the nervous system, and produces neuropharmacological and behavioral effects. Clinical studies suggest that cotinine is psychoactive in humans. However, reviewing evidence regarding mechanisms underlying effects of cotinine provides a mixed picture with a lack of consensus. Therefore, more research is warranted in order to provide better insight into the actions of cotinine and its contribution to tobacco addiction.