Essential Oil Constituents as Anti-Inflammatory and Neuroprotective Agents: An Insight through Microglia Modulation.

Microglia are key players in the brain's innate immune response, contributing to homeostatic and reparative functions but also to inflammatory and underlying mechanisms of neurodegeneration. Targeting microglia and modulating their function may have therapeutic potential for mitigating neuroinflammation and neurodegeneration. The anti-inflammatory properties of essential oils suggest that some of their components may be useful in regulating microglial function and microglial-associated neuroinflammation. This study, starting from the ethnopharmacological premises of the therapeutic benefits of aromatic plants, assessed the evidence for the essential oil modulation of microglia, investigating their potential pharmacological mechanisms. Current knowledge of the phytoconstituents, safety of essential oil components, and anti-inflammatory and potential neuroprotective effects were reviewed. This review encompasses essential oils of Thymus spp., Artemisia spp., Ziziphora clinopodioides, Valeriana jatamansi, Acorus spp., and others as well as some of their components including 1,8-cineole, ß-caryophyllene, ß-patchoulene, carvacrol, ß-ionone, eugenol, geraniol, menthol, linalool, thymol, α-asarone, and α-thujone. Essential oils that target PPAR/PI3K-Akt/MAPK signalling pathways could supplement other approaches to modulate microglial-associated inflammation to treat neurodegenerative diseases, particularly in cases where reactive microglia play a part in the pathophysiological mechanisms underlying neurodegeneration.

Chemical Composition and Cytotoxicity Evaluation of Artemisia judaica L. Essential Oil from Saudi Arabia.

Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses were conducted on essential oil extracted from Saudi Arabian Artemisia judaica L. (A. judaica) aerial parts, resulting in the identification of 58 constituents, representing 93.0% of the total oil composition. The oil primarily consisted of monoterpenes (38.6%), sesquiterpenes (14.1%), and other compounds such as ethyl esters and cyclic ketones (40.3%). The main components identified were piperitone (16.5%), ethyl cinnamate (12.9%), and camphor (9.7%). Multivariate statistical analyses (MVAs), including principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) analysis, were employed to compare the chemical makeup of this oil with 20 other A. judaica oils from various regions. The study revealed distinct clusters, highlighting unique chemotypes and geographic variations. Particularly, the oil from the current study demonstrated a specialized chemical profile with significant concentrations of specific compounds, contributing significantly to its distinctiveness. Further cytotoxicity testing on RAW264.7 macrophages suggested that concentrations below 20 µg/mL of A. judaica oil are suitable for future pharmacological investigations. This study provides valuable insights into the chemical diversity, geographic variations, and potential biomedical applications of these essential oils.

Synthesis of Small Libraries of Natural Products: Part II: Identification of a New Natural Product from the Essential Oil of Pleurospermum austriacum (L.) Hoffm. (Apiaceae).

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 P. austriacum 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.

In vitro activity of essential oils against adult and immature stages of Ctenocephalides felis felis.

Essential oils (EOs) are considered a new class of ecological products aimed at the control of insects for industrial and domestic use; however, there still is a lack of studies involving the control of fleas. Ctenocephalides felis felis, the most observed parasite in dogs and cats, is associated with several diseases. The aim of this study was to evaluate the in vitro activity, the establishment of LC50 and toxicity of EOs from Alpinia zerumbet (Pers.) B. L. Burtt & R. M. Sm, Cinnamomum spp., Laurus nobilis L., Mentha spicata L., Ocimum gratissimum L. and Cymbopogon nardus (L.) Rendle against immature stages and adults of C. felis felis. Bioassay results suggest that the method of evaluation was able to perform a pre-screening of the activity of several EOs, including the discriminatory evaluation of flea stages by their LC50. Ocimum gratissimum EO was the most effective in the in vitro assays against all flea stages, presenting adulticide (LC50 = 5.85 µg cm-2), ovicidal (LC50 = 1.79 µg cm-2) and larvicidal (LC50 = 1.21 µg cm-2) mortality at low doses. It also presented an excellent profile in a toxicological eukaryotic model. These findings may support studies involving the development of non-toxic products for the control of fleas in dogs and cats.

Pharmacological Evaluation of Artemisia cina Crude CO2 Subcritical Extract after the Removal of Santonin by Means of High Speed Countercurrent Chromatography.

Artemisia species are highly important due to their economic significance as medicines, fodder and food. Artemisia cina is an endemic species to Kazakhstan. In folk medicine, water extract of A. cina was used in the treatment of bronchial asthma while the alcohol extract has larvicidal and antituberculosis activity. The most common and most extensively studied compound from this species is the terpenoid santonin. The toxicity of this compound occurs at the doses of 60 mg for children and 200 mg for adults causing among other issues xanthopsia, leading to blindness. Having this in mind, the main idea of this work was to remove santonin from the crude extract and to check if the santonin-free extract would still be of any pharmacological importance. A CO2 subcritical extract was chromatographed using high-speed countercurrent chromatography (HSCCC) for the removal of santonin. The santonin-free CO2 subcritical extract (SFCO2E) as well as the isolated compound pectolinarigenin, a flavonoid, were assessed for their pharmacological actions. From the results obtained we can safely suggest that HSCCC is an efficient methodology to completely remove santonin from the CO2 subcritical extract. It was also possible to observe promising antinociceptive and anti-inflammatory activities for both SFCO2E and pectolinarigenin at concentrations that can justify the production of a phytomedicine with this endemic plant from Kazakhstan.

Chemical composition and enzyme inhibition of Phytolacca dioica L. seeds extracts.

Phytolacca, which belongs to the family of Phytolaccaceae, are known for their use in popular medicine. Bioactivity of five extracts from Phytolacca dioica seeds were evaluated in four bioassays. A selected group of compounds from the extract that displayed the best bioactivity was analysed. The ethyl acetate extract (EAE) possessed the highest content of phenolics, the highest inhibitory activity on the tyrosinase and xanthine oxidase enzymes and showed a high antioxidant activity. HPLC-DAD-MS was employed to identify the phenolics profile of the most active one (EAE). HSCCC analysis of the EAE led to the isolation of phytolaccoside B and a mixture of 4 isomers, isoamericanol B1, B2, C1 and C2. These isoamericanol isomers presented activity against tyrosinase and xanthine oxidase. Our results revealed for the first time an interesting biological activity of the extract and isolated compounds from P. dioica seeds, which could be considered as a source of bioactive molecules.

Study on the Antinociceptive Activity and Mechanism of Action of Isolated Saponins from Siolmatra brasiliensis (Cogn.) Baill.

Infusions of roots of Siolmatra brasiliensis (Cogn.) Baill, ("taiuiá", "cipó-tauá") are used for toothache pain and ulcers. We aimed to study the antinociceptive effects and identify the possible mechanism of action of this plant and its isolated substances (cayaponoside A1, cayaponoside B4, cayaponoside D, and siolmatroside I). Hydroethanol extract (HE), ethyl acetate fraction (EtOAc), and isolated saponins were evaluated in chemical and thermal models of pain in mice. Animals were orally pretreated and evaluated in the capsaicin- or glutamate-induced licking and in the hot plate tests. The antinociceptive mechanism of action was evaluated using the hot plate test with the following pretreatments: Atropine (cholinergic antagonist), naloxone (opioid antagonist), or L-NAME (nitric oxide synthase inhibitor). All extracts and isolated saponins increased the area under the curve in the hot plate test. Tested substances induced a higher effect than the morphine-treated group. Our data suggest that stems of S. brasiliensis and their isolated substances present antinociceptive effects. Cholinergic and opioidergic pathways seem to be involved in their mechanism of action. Taken together our data corroborate the traditional use of the plant and expands the information regarding its use.

Development and characterization of poly(lactic-co-glycolic) acid nanoparticles loaded with copaiba oleoresin.

Copaiba oleoresin (CPO), obtained from Copaifera landgroffii, is described as active to a large number of diseases and more recently in the endometriosis treatment. In this work, poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing CPO were obtained using the design of experiments (DOE) as a tool to optimize the production process. The nanoparticles optimized by means of DOE presented an activity in relation to the cellular viability of endometrial cells. The DOE showed that higher amounts of CPO combined with higher surfactant concentrations resulted in better encapsulation efficiency and size distribution along with good stability after freeze drying. The encapsulation efficiency was over 80% for all produced nanoparticles, which also presented sizes below 300 nm and spherical shape. A decrease in viability of endometrial stromal cells from ectopic endometrium of patients with endometriosis and from eutopic endometriotic lesions was demonstrated after 48 h of incubation with the CPO nanoparticles. The nanoparticles without CPO were not able to alter the cell viability of the same cells, indicating that this material was not cytotoxic to the tested cells and suggesting that the effect was specific to CPO. The results indicate that the use of CPO nanoparticles may represent a promising alternative for the treatment of endometriosis.

Pharmacological, toxicological and phytochemical analysis of Spondias dulcis parkinson.

Spondias dulcis Parkinson have been used in traditional medicine in Asia, Oceania, and South America, for different diseases conditions and as a functional food. The scientific literature described as different potential pharmacology such as antioxidant, anti-inflammatory, antimicrobial, thrombolytic and enzymatic inhibitor. This study aimed to: (1) establish the pharmacological activity in intestinal motility in vivo and antioxidant activity in vitro; (2) perform the acute toxicology test in mouse; (3) characterize the phytochemical profile based on counter-current chromatography (CCC) and NMR analysis. The results revealed a laxative effect of S. dulcis extract and a high antioxidant activity (IC50 = 5.10 for DPPH assay and 14.14 for hydrogen peroxide scavenging test). No side effects were observed in the oral acute toxicity test for a dose up to 2000 mg/kg. The chemical profile was identified by CCC and NMR, and the comparison of the data obtained with previous literature revealed the presence of the flavonoid rutin (Quercetin-3-O-rutinoside) in the extract.

Amazon Rainforest Hidden Volatiles-Part I: Unveiling New Compounds from Acmella oleracea (L.) R.K. Jansen Essential Oil.

Motivated by the culinary and ethnopharmacological use of Acmella oleracea (L.) R.K. Jansen, this study aimed to unveil new chemical compounds from its essential oil (EO). Acmella oleracea, known for its anesthetic and spicy properties, has been used in traditional medicine and cuisine, particularly in Northern Brazil. Through a detailed GC-MS analysis, 180 constituents were identified, including 12 tentatively identified long-chain α-keto esters of various acids. Additionally, 18 new esters were synthesized for structural verification. This research expands the known chemical diversity of A. oleracea EO, providing a basis for potential pharmacological applications. The identification of new natural products, including homologs and analogs of acmellonate, underscores the EO's rich chemical profile and its potential for novel bioproduct development.

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice.

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

Effects of methyl and isopropyl N-methylanthranilates from Choisya ternata Kunth (Rutaceae) on experimental anxiety and depression in mice.

Choisya ternata Kunth (Rutaceae) is a plant species used in Mexican folk medicine for its antispasmodic and simulative properties. Recently, we identified a new alkaloid, isopropyl N-methylanthranilate, and a related one, methyl N-methylanthranilate, from the essential oil of this species and have proven them to possess antinociceptive activity even at 0.3 mg/kg. In the present study, anxiolytic and antidepressant effects of the two compounds have been studied in open field, horizontal wire, light/dark, forced swimming and tail suspension tests, as well as the effect on the onset and duration of diazepam-induced sleep in BALB/c mice. The volatile alkaloids (50-200 mg/kg, administered intraperitoneally), without having a muscle relaxant effect, caused a significant increase in the time the animals spent in an unsecured and putatively dangerous area when compared with the control group but had no effect on the number of crossings between the light/dark compartments. In addition to this anxiolytic activity, a significantly antidepressant-like effect was apparent at all tested doses, which was not due to an increase in locomotive activity. The anthranilates administered on their own did not induce sleep in mice but significantly prolonged the diazepam-induced sleep, in a dose-dependent way, suggesting an interaction with the gamma-aminobutyric acid receptor complex.

Medicinal Plants: Advances in Phytochemistry and Ethnobotany.

Prance once defined Ethnobotany as an interdisciplinary Science combining Anthropology and Botany [...].

Capparis cartilaginea decne (capparaceae): isolation of flavonoids by high-speed countercurrent chromatography and their anti-inflammatory evaluation.

Introduction: Capparis cartilaginea Decne. (CC) originates from the dry regions of Asia and the Mediterranean basin. In traditional medicine, tea of CC leaves is commonly used to treat inflammatory conditions such as rheumatism, arthritis, and gout. Due to the limited studies on the phytochemistry and biological activity of CC compared to other members of the Capparaceae family, this work aims to: 1) Identify the chemical composition of CC extract and 2) Investigate the potential anti-inflammatory effect of CC extract, tea and the isolated compounds. Methods: To guarantee aim 1, high-speed countercurrent chromatography (HSCC) method; Nuclear Magnetic Resonance (NMR) and High-Performance Liquid Chromatography coupled to Electrospray Ionisation and Quadrupole Time-of-Flight Mass Spectrometry (HPLC-ESIQTOF-MS/MS) were employed for this purpose. To guarantee aim 2, we studied the effect of the isolated flavonoids on matrix metalloproteinases (MMPs) -9 and -2 in murine macrophages. Molecular docking was initially performed to assess the binding affinity of the isolated flavonoids to the active site of MMP-9. Results and discussion: In silico model was a powerful tool to predict the compounds that could strongly bind and inhibit MMPs. CC extract and tea have shown to possess a significant antioxidant and anti-inflammatory effect, which can partially explain their traditional medicinal use.

Wax Composition of Serbian Dianthus spp. (Caryophyllaceae): Identification of New Metabolites and Chemotaxonomic Implications.

Although ethnopharmacologically renowned, wax constituents of Dianthus 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 Dianthus taxa (Dianthus carthusianorum, D. deltoides, D. giganteus subsp. banaticus, D. integer subsp. minutiflorus, D. petraeus, and D. superbus) and one Petrorhagia taxon (P. prolifera) from Serbia. Seventeen of these constituents (nonacosyl benzoate, additional 12 benzoates with anteiso-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 ß-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 Dianthus taxa's surface waxes is subject to both genetic and ecological factors, whereas the latter seemingly takes a more important role for the studied Dianthus samples.

Characterization of Larix decidua Mill. (Pinaceae) oleoresin's essential oils composition using GC-MS.

Introduction: Larch oleoresin has been described regarding several biological activities and medicinal applications, such as wound healing and treatment of ulcers, but little is known about its chemical composition. Material and methods: Eight oleoresins from Larix decidua Mill. obtained from four companies and one adulterated control were therefore investigated to determine their content of essential oils and to verify possible differences in their composition in relation to the harvest and manufacturing processes. Essential oils (EOs) were isolated by distillation and the yield was analysed. Results and discussion: The yield of EO varied among all samples. The yield of the pure larch samples covered a range of 7.8% to 15.5%. A higher yield (19.0%) was observed for adulterated control, which contained oleoresins from different Pinaceae trees. Age of samples had no impact on yield. However, there was a significant statistical variation (p<0.05) in the yields of the mid-summer oleoresins (>10%) compared to early or late summer (<10%), emphasising the importance of the time of collection. Samples were subsequently analysed by GC-MS. EO samples confirmed the presence of various chemical classes, such as monoterpenes, sesquiterpenes, and diterpenes. α-pinene was the compound with the highest concentrations (>50%), followed by ß-pinene (>6%), D-limonene (>2.5%), α-terpineol (>0.9%), ß-myrcene (>0.2%), and 3-carene (>0.05%). Samples were grouped using multivariate data analysis (MVDA) with respect to the chemical variation between the oleoresins' EOs. The resulting four clusters were named low (low yield obtained for the samples), mixed (mixed oleoresin from different Pinaceae species, adulteration control), old (old oleoresin kept in the institute), and normal (other oleoresins) samples, each presenting distinct chemical biomarkers. There were considerable differences between site and time of collection. Essential oil yield did not always meet requirements as defined by the German Homeopathic Pharmacopoeia. In addition, adulterated or aged samples could be identified as compared to pure and fresh larch oleoresins. Conclusion: We conclude that larch oleoresin used for pharmaceutical applications has to be carefully analysed and standardised to guarantee reproducible product quality.

Campomanesia lineatifolia Ruiz & Pavón (Myrtaceae): Isolation of major and minor compounds of phenolic-rich extract by high-speed countercurrent chromatography and anti-inflammatory evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Campomanesia lineatifolia Ruiz & Pavón (Myrtaceae), an edible species found in Brazilian Forest, possesses leaves that are traditionally used for the treatment of gastrointestinal disorders in Brazil. Extracts of C. lineatifolia are rich in phenolics and exhibit antioxidant, and gastric antiulcer properties. Furthermore, Campomanesia spp. have been described to possess anti-inflammatory properties, but studies related to chemical constituents of C. lineatifolia are scarce in the literature. AIM OF THE STUDY: This work aims to identify the chemical composition of the phenolic-rich ethanol extract (PEE) from C. lineatifolia leaves and evaluate the anti-inflammatory activity that could be related to its ethnopharmacological use. MATERIALS AND METHODS: The high-speed countercurrent chromatography (HSCCC), using an isocratic and a step gradient elution method, and NMR, HPLC-ESI-QTOF-MS/MS were used to isolate and identify the chemicals of PEE, respectively. Lipopolysaccharide-(LPS)-stimulated THP-1 cells were used to evaluate the anti-inflammatory activities from PEE and the two majority flavonoids isolated by measure TNF-α and NF-κB inhibition assays. RESULTS: Fourteen compounds were isolated from the PEE, further identified by NMR and HPLC-ESI-QTOF-MS/MS, twelve of them are new compounds, and two others are already known for the species. The PEE, quercitrin and myricitrin promoted a concentration-dependent inhibition of TNF-α, and PEE promoted an inhibition of NF-κB pathway. CONCLUSIONS: PEE from C. lineatifolia leaves demonstrated significant anti-inflammatory activity that may be related to the traditional use to treat gastrointestinal disorders.

Choisyaternatine, a new alkaloid isolated from Choisya ternata.

One novel compound was isolated from the hexane extract of Choisya ternata Kunth. leaves, choisyaternatine (1), together with the known compounds tecleamaniensine A (2), lup-20(29)-en-3ß-ol (lupeol) (3), lup-20(29)-en-3ß,24-diol (4), ß-sitosterol glucoside (5), and skimmianine (6), plus the following known compounds from the dichloromethane extract, choisyine (7) and 6-methoxy-7,8-methylenedioxycoumarin (8). Compounds 2-5 are reported for the first time in this species. The structures of isolated compounds were elucidated by extensive spectroscopic analyses and comparison with previously reported spectroscopic data. The structure of choisyaternatine was further confirmed based on X-ray data analysis.

Volatiles of Capparis cartilaginea Decne. from Saudi Arabia.

In this study, GC and GC-MS analysis of the essential oil obtained from the leaves of Saudi Arabian Capparis cartilaginea Decne. (CC) allowed for the identification of 41 constituents, comprising 99.99% of the total oil composition. The major compounds identified were isopropyl isothiocyanate (31.0%), 2-methylbutanenitrile (21.4%), 2-butyl isothiocyanate (18.1%), isobutyronitrile (15.4%), and 3-methylbutanenitrile (8.2%). The chemical composition of the derived oil and 12 additional oils obtained from selected Capparis taxa were compared using multivariate analyses including principal component analysis (PCA) and agglomerative hierarchical cluster analysis (AHC). The results of the statistical analyses of this particular data set pointed out that isopropyl isothiocyanate could be potentially used as a valuable infrageneric chemotaxonomical marker for CC. Moreover, the results distinctly separate CC from other members of its genus on the basis of its components. In addition, environmental and geographical stressors may be implicated in the essential oil profile of plants found within the genus Capparis.

A Scoping Review on the Therapeutic Potential of Resin From the Species Larix decidua Mill. [Pinaceae] to Treat Ulcerating Wounds.

Malignant ulcerating wounds or neoplastic lesions are a considerable burden for patients suffering from advanced cancer. These wounds have no effective treatment and are very difficult to manage. The present review summarizes evidence in support of a hypothesis put forward in anthroposophic medicine, which suggests a beneficial role of resin from the species Larix decidua Mill. [Pinaceae] for treating such wounds. A systematic search strategy was performed using the databases PubMed, EMBASE and SciFinder. The included publications described the chemical composition of this species, as well as in vitro, in vivo, and ex vivo experiments using plant extracts and isolated compounds. The results show that among the phytochemical classes, terpenoids were the major components of this species, especially in the resin. The summarized biological experiments revealed antimicrobial, antioxidant and anti-inflammatory effects, with promising potential for the extracts and isolated compounds. However, the molecular mechanisms and toxicological effects are as of yet not conclusively evaluated. From the data of our study, we can conclude that L. decidua might indeed have a promising potential for the treatment of malignant wounds, but definitive information that can prove its effectiveness is still lacking. We therefore suggest that future efforts should be dedicated to the evaluation of L. decidua resin's therapeutic use considering its antiseptic action and proposed wound healing properties.