This work is focused on the characterization of the composition of a CO2 supercritical fluid extract of Aquilaria sinensis (Chinese agarwood) collected in the Dongguan area (China) and infected by ...mechanical methods. The constituents of this extract were analyzed by gas chromatography–mass spectrometry (GC-MS) and quantified accurately by gas chromatography with a flame ionization detector (GC-FID), using an internal reference and predicted response factors. Since a significant number of components of this extract remained non-identified after the initial GC-MS analysis of the whole extract, its fractionation by chromatography on silica gel helped to characterize several additional constituents by isolation and structural analysis by NMR spectroscopy. The main components are the classical agarwood chromones (Flindersia chromone and its mono-, di-, and trimethoxylated analogues (respectively, 11.01% and 0.11–4.02%) along with sesquiterpenic constituents typically found in agarwood essential oils, like baimuxinal (1.90%) and kusunol (1.24%), as well as less common selinane dialdehydes (1.58–2.27%) recently described in the literature. Moreover, the structure and stereochemistry of a new sesquiterpenic alcohol, 14β,15β-dimethyl-7αH-eremophila-9,11-dien-8β-ol (0.67%), was determined unambiguously by the combination of structural analysis (NMR, MS), hemisynthesis, and total synthesis, leading to dihydrokaranone and a neopetasane epimer.
Herein, comprehensive data of NMR, MS, IR, and gas chromatography (RI) obtained by GC-MS on commonly used capillary columns of different polarity (non-polar DB-5MS and polar HP-Innowax) of a series ...of esters of all constitutional isomers of hexanoic acid with a homologous series of ω-phenylalkan-1-ols (phenylmethanol, 2-phenylethanol, 3-phenylpropan-1-ol, 4-phenylbutan-1-ol, and 5-phenylpentan-1-ol) and phenol, in total 48 chemical entities, were collected. The created synthetic library allowed the identification of a new constituent of the
essential oil (3-phenylpropyl 2-methylpentanoate). The accumulated spectral and chromatographical data, as well as the established correlation between RI values and structures of regioisomeric hexanoates, provide (phyto)chemists with a tool that will make future identification of related natural compounds a straightforward task.
Among the fewest drugs discovered are those belonging to the class of anxiolytics. Although some drug targets for anxiety disorders are established, it is hard to modify and selectively choose the ...active principle for those targets. Thus, the ethnomedical approach to treating anxiety disorders remains one of the most prevalent ways for (self)managing the symptoms. Melissa officinalis L. (lemon balm) has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, especially dose related to restlessness.
This work aimed to evaluate the anxiolytic activity, in several in vivo models, of the essential oil extracted from Melissa officinalis (MO) and its main constituent citronellal, a widespread plant utilized for managing anxiety.
In the present study several animal models were used to assess MO anxiolytic potential in mice. The effect of the MO essential oil applied in doses ranging from 12.5 to 100 mg/kg was estimated in light/dark, hole board, and marble burying tests. In parallel doses of citronellal corresponding to the ones in the MO essential oil were applied to animals to determine if this is the activity carrier.
The results indicate that the MO essential oil exerts anxiolytic potential in all three experimental settings by significantly altering the traced parameters. The effects of citronellal are somewhat inconclusive and should not be interpreted only as anxiolytic but rather as a combination of anti-anxiety and motor-inhibiting effects.
In conclusion, we could say that the results of the present study provide a base for future mechanistic studies that would evaluate the activity of M. officinalis essential oil on various neurotransmitter systems involved in the generation, propagation, and maintenance of anxiety.
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•Melissa officinalis essential oil might possess promising anxiolytic effects.•Citronellal and M. officinalis exert in vivo anxiolytic-like activity.•In a dose of 12.5 mg/kg M. officinalis essential oil acts as anxiolytic.•The anxiolytic activity of citronellal might be due to motor inhibition.
Despite being renowned for its volatiles, the data on the toxicity of the essential oil of lemon balm (Melissa officinalis L., Lamiaceae) is rather limited compared to its solvent/water-soluble ...extractibles. In this study, the aerial parts essential oil of M. officinalis, with over 130 constituents identified herein, 26 of which detected for the first time, was investigated for acute oral toxicity in BALB/c mice. The oil, composed of predominantly monoterpene aldehydes, citronellal (21.2–21.8%), neral (17.8–18.4%), and geranial (22.9–23.5%), which were assayed in parallel with the oil in some tests, induced significant changes in animal behavior, as well as altered biochemical parameters reflecting liver and kidney functions. Different pathological changes in the stomach, duodenum, liver, and kidneys were detected when the oil was administered in doses higher than 1 g kg−1. A depletion in the liver/kidney antioxidant capacities and an increased rate of lipid peroxidation was noted for animals treated with lemon balm oil. The calculated value of the oral LD50 in BALB/c mice (2.57 g kg−1) infers that the essential oil is only moderately toxic.
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•Twenty-six compounds are reported here for the first time as constituents of M. officinalis essential oil.•Oral application of lemon balm essential oil causes significant changes in mice behavior, and liver and kidney functions.•Above 1 g kg−1 (p.o.), different pathological changes in the stomach, duodenum, liver, and kidneys were detected.•The essential oil produced a depletion of liver/kidney antioxidant capacities and increased the rate of lipid peroxidation.•The determined oral LD50 in BALB/c mice (2.57 g kg−1) suggests that the essential oil is only moderately toxic.
Besides psyche-related symptoms, patients with anxiety disorders can have a large number of somatic symptoms as well. Although the treatment of these disorders is mainly focused on resolving their ...mental component, one cannot neglect the need for the treatment of accompanying somatic symptoms. Melissa officinalis L. (lemon balm), in various formulations, has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, and its use is considered relatively safe.
Aim of the study: In the present study, the activity of M. officinalis (MO) essential oil was evaluated in several in vitro and in vivo models mimicking or involving anxiety-related somatic symptoms.
To address the effect of MO essential oil on the gastrointestinal and heart-related symptoms accompanying anxiety disorders, in vitro models were utilized that follow the function of the isolated mouse ileum and atria tissues, respectively, after exposure to MO essential oil. Effects of MO essential oil on BALB/c mice motor activity was estimated using the open field, rota-rod, and horizontal wire tests. Additionally, the essential oil was assayed for its potential in inhibiting acetylcholinesterase activity.
The performance of mice treated with 25 mg/kg of the oil showed a statistically significant decrease in the motor impairment arising from acute anxiety (open field test), while there was a prolonged latency and a reduction of the frequency of falling from a rotating rod and/or a horizontal wire (signs of muscle weakness/spasms). Concentrations of the essential oil higher than 1 μg/mL were found to inhibit both spontaneous and induced ileum contractions. Moreover, the essential oil and citronellal were found to decrease isolated mouse atria contraction frequency, as well as contraction force. However, the oil was found to be a very weak acetylcholinesterase inhibitor.
The modulation of anxiety-related symptoms by the oil was found not to be mediated through the inhibition of the acetylcholinesterase, nonetheless, the mechanistic studies involving the ileum and cardiac tissues, revealed that the activity of MO and citronellal might be related to the modification of either voltage-gated Ca2+ channels or muscarinic receptors. Mice locomotion, balance, and muscle strength were not impacted by the essential oil; however, its main constituent, citronellal, was found to exert a certain degree of muscle function inhibition. All these results suggest that the activity of MO essential oil arises from synergistic and/or antagonistic interactions of its constituents, and is not completely dependent on the oil's main constituent.
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•Melissa officinalis (MO) is utilized for different psyche-related disorders including anxiety.•MO essential oil and citronellal were tested in models involving anxiety-linked somatic symptoms.•MO essential oil and citronellal were found to inhibit spontaneous and induced ileum contractions.•They decreased heart rate and force of contraction but differently affected mice motor function.•They were both weak acetylcholine inhibitors but act via voltage-gated Ca2+ channels.
L-Glutamic acid decarboxylase (GAD) is an enzyme that ensures the balance between the levels of two neurotransmitters, γ-aminobutyric acid (GABA) and L-glutamic acid (L-Glu), necessary for proper ...brain functioning. A reduction in the concentrations of GABA and/or GAD activity has been implicated in the symptoms associated with epilepsy, which could be plausibly alleviated by the application of GAD activators. As any unnecessary interference in GAD catalytic activity could be detrimental, it is important to study whether CNS (or other) drug candidates act on GAD or not. The ability to identify and reduce this risk early could significantly improve the process of drug development. Although many methods for measuring GAD activity in various biological samples have been described, only few (such as manometric and radiometric) were adopted as in vitro assays for the screening of potential GAD inhibitors/activators. However, these methods require specialized equipment and/or an expensive radiolabeled substrate, and may have sensitivity and/or reliability issues. Therefore, this study aimed to develop an HPLC-DAD-based assay that would allow a simple and more accurate measurement of GAD inhibition or activation using unpurified mice or rat brain homogenates. This assay is based on the quantification of GABA, formed during the enzymatic reaction, after its derivatization with dansyl chloride. Various parameters were evaluated to optimize the assay procedure (e.g. homogenate volume, incubation time, DMSO content, GAD, GABA, and dansyl-GABA stabilities). This assay was validated for pharmacological screenings using 3-mercaptopropionic acid and gallic acid and GAD obtained from different experimental animals.
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•Glutamate decarboxylase (GAD) regulates the interconversion of L-Glu to GABA.•Only 2 methods with serious issues are in use for in vitro measurements of GAD.•An improved simple HPLC-based assay for GAD activity was developed.•No need for specialized equipment, expensive reagents, and pure enzyme use.•Possibility of sample storage and different enzyme sources utilization.
•Previous chemical and toxicological data on the ethnomedicinally valued species Achillea falcata L. (Asteraceae) are scarce.•As confirmed by GC-MS and extensive NMR, trans-sabinol and its esters are ...the dominant A. falcata volatiles.•trans-Sabinyl formate and tiglate represent newly discovered natural products.•These compounds have moderate acute toxicity and acetylcholinesterase inhibitory activity.•Three complementary antinociceptive assays showed that the esters influence both the peripheral and central nervous systems.
Herein we report on the comprehensive chemical analysis of the essential oils obtained from above- and underground parts of a previously unreported chemotype of Achillea falcata L. (Asteraceae) and, for the first time, on the biological/toxicological profile of its dominant/newly discovered volatile metabolites. Detailed spectral analyses, in combination with chemical synthesis and theoretical study, of selected constituents, enabled the identification of trans-sabinol and its esters – the formate, tiglate (new compounds), acetate, butanoate, isobutanoate, 2-methylbutanoate and 3-methylbutanoate – in both aerial and underground parts of A. falcata. Evaluation of acute toxicity in Artemia salina model, in vitro and in silico (molecular docking) evaluation of acetylcholinesterase inhibitory activity and in vivo (mice) evaluation of antinociceptive activity (hot plate, tail immersion and acetylcholine-induced abdominal writhing tests) of trans-sabinol and its esters suggested that they may interact with different targets in crustacean/mammalian organisms. Alongside moderate acute toxicity (LD50 (48 h) = 0.03–0.26 mmol/L), the tested compounds exert influence on both the peripheral and central nervous systems (in the hot plate test, trans-sabinyl tiglate, at 50 mg/kg, produced a 140% baseline increase 15 min after the treatment) and to moderately inhibit acetylcholinesterase (at the concentration of 20 µg/mL, these compounds caused a reduction of acetylcholinesterase activity up to 40%).
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•Eugenyl angelate and eugenyl 2-methylbutanoate are new compounds found in Anthemis segetalis essential oil.•A small combinatorial library comprised of the new compounds and related ...regioisomeric compounds was screened for toxicity.•New natural compounds have low toxicity against Artemia salina and low cytotoxicity against fibroblast and melanoma cells.•They are also weak antimicrobials and acetylcholinesterase inhibitors.•Intake of these esters in the form of A. segetalis botanical drug would not cause undesirable/adverse effects.
To determine the exact structure of previously tentatively identified minor essential-oil constituents of a Chamomile species (Antemis segetalis Ten. (Asteraceae)), we have synthesized a small combinatorial library of 54 regioisomeric allylmethoxyphenyl pentanoates and 2-pentenoates (49 completely new compounds). GC–MS in combination with 1D- and 2D-NMR analyses of the library compounds provided unambiguous data that led to a straightforward identification of the mentioned A. segetalis constituents as eugenyl angelate, 2-methylbutanoate and 3-methylbutanoate (0.21, 0.22, and 0.13mg/100g of fresh plant material, respectively). To assess the safety and potential beneficial pharmacological uses of these naturally occurring esters and several other library compounds (these were tested to provide relevant data for a SAR (structure–activity relationship) analysis), we have studied the effect of these compounds in several models of toxicity (acute toxicity against Artemia salina, cytotoxicity against two cell lines (fibroblast and melanoma)), as well as their acetylcholinesterase inhibitory and antibacterial activities. Anthemis segetalis constituents showed low to moderate activity in all tests. The obtained results suggest that the intake of these compounds in naturally available amounts, on their own, would probably not represent a risk to human health but the possible adverse interactions with the plant matrix should not be neglected.
A recent identification of eugenyl (allylmethoxyphenyl) esters as Anthemis segetalis Ten. (Asteraceae) essential oil constituents, accomplished by means of organic synthesis, motivated us to expand ...the existing synthetic library with an aim to examine the generality of structure‐chromatographic property relationships within this series of volatiles. Herein, the design, synthesis, gas–chromatographic and spectral characterization of members of a library of 85 allylmethoxyphenyl esters (64 are completely new) were described. Analysis of experimentally obtained RI data showed that esters of the same acid and different allylmethoxyphenols always elute in the same order from an apolar gas chromatography (DB‐5MS) column: 2‐allyl‐6‐methoxyphenyl < 2‐allyl‐3‐methoxyphenyl < 2‐allyl‐5‐methoxyphenyl < 2‐allyl‐4‐methoxyphenyl < 4‐allyl‐2‐methoxyphenyl esters. Based on the obtained RI values, several quantitative structure–property relationship models were built up that correlated several easily available parameters (e.g. Wiener WI, Balaban BI, and molecular topological MTI indices) of the mentioned esters and their RI data. The generated various quantitative structure–property relationships models (equations that predict RIs of esters of different regioisomers of allylmethoxyphenols with the same acids and the ones that predict RIs of esters of different acids with the same allylmethoxyphenols) were tested on data of previously known related esters. RI data of esters of allylmethoxyphenol regioisomers could be successfully predicted based on 1D topological indices, such as the Balaban, Wiener, and molecular topological indices. Together with RI and MS data accumulated in this work, these models represent a new and simple tool for the identification of allylmethoxyphenyl esters that might potentially represent new or rare natural products.
Herein, the design, synthesis, gas chromatographic, and spectral characterization of members of a library of allylmethoxyphenyl esters (85 compounds, the majority of which (64) are new compounds) were described. The obtained quantitative structure–property modeling models represent, together with RI and MS data summarized in this work, a new and simple tool for the identification of allylmethoxyphenyl esters that might potentially represent new or rare (often erroneously identified or missed out during standard analyses) natural products.
Although ethnopharmacologically renowned, wax constituents of
species were sporadically studied. A combination of GC-MS analysis, synthesis, and chemical transformations enabled the identification of ...275 constituents of diethyl-ether washings of aerial parts and/or flowers of six
taxa (
,
,
subsp.
,
subsp.
,
, and
) and one
taxon (
) from Serbia. Seventeen of these constituents (nonacosyl benzoate, additional 12 benzoates with
-branched 1-alkanols, eicosyl tiglate, triacontane-14,16-dione, dotriacontane-14,16-dione, and tetratriacontane-16,18-dione) and two additional synthesized eicosyl esters (angelate and senecioate) represent completely new compounds. The structures of the tentatively identified β-ketones were confirmed by analysis of the mass fragmentation of the corresponding pyrazoles and silyl enol ethers obtained by transformations of crude extracts and extract fractions. Silylation allowed the identification of 114 additional constituents, including a completely new natural product (30-methylhentriacontan-1-ol). The results obtained by multivariate statistical analyses showed that the chemical profile of
taxa's surface waxes is subject to both genetic and ecological factors, whereas the latter seemingly takes a more important role for the studied
samples.
