A Review of the Phytochemistry, Traditional Uses and Biological Activities of the Essential Oils of Genus Teucrium.

The genus Teucrium is a large and polymorphic genus of the Lamiaceae family distributed in mild climate zones, particularly in the Mediterranean basin and Central Asia. Studies of nonvolatile constituents of Teucrium species showed that they are a rich source of neo-clerodane diterpenoids, considered as chemotaxonomic markers of the genus. In addition to the nonvolatile metabolites, there has been a large interest in the essential oils of this genus. In this review, a complete survey of the chemical composition and biological properties of the essential oils isolated from Teucrium taxa is provided. In traditional medicine, since ancient times, species of this genus have been widely implemented for their biological properties, including antimicrobial, anti-inflammatory, antispasmodic, insecticidal, anti-malaria, etc. Therefore, a complete review of all of the traditional uses of Teucrium taxa are also reported.

The Essential Oil Compositions of Three Teucrium Taxa Growing Wild in Sicily: HCA and PCA Analyses.

The chemical composition and the qualitative and quantitative variability of the essential oils of three taxa belonging to the Teucrium genus were studied. The investigated taxa, that grow wild in Sicily, were Teucrium flavum L. (section Chamaedrys (Mill.) Scheb.), Teucrium montanum and Teucrium capitatum L. of section Polium (Mill.) Scheb. Essential oils were extracted by hydrodistillation and analyzed by GC-MS. In total, 74 compounds were identified. Sesquiterpene hydrocarbons were found to be the main group for T. flavum (48.3%). T. capitatum consisted essentially of monoterpene hydrocarbons (72.7%), with α-pinene (19.9%), ß-pinene (27.6%) and sylvestrene (16.6%) as the most abundant compounds whereas ledene oxide (12.1%), epiglobulol (13.5%) and longifolenaldehyde (14.5%) were identified as the main constituents among the oxygenated sesquiterpenes (63.5%) of T. montanum. Furthermore, a complete literature review on the composition of the essential oils of all the other accessions of these Teucrium taxa, studied so far, was performed. Hierarchical Cluster Analysis (HCA) and Principal Component Analyses (PCA) were used in order to demonstrate geographical variations in the composition of the essential oils.

Ferulago nodosa Subsp. geniculata (Guss.) Troia & Raimondo from Sicily (Italy): Isolation of Essential Oil and Evaluation of Its Bioactivity.

Ferulago nodosa (L.) Boiss. (Apiaceae) is a species occurring in the Balkan-Tyrrhenian area. The object of the present study is Sicilian F. nodosa subsp. geniculata (Guss.) Troia & Raimondo, classified as an endemic F. nodosa subspecies. Aerial parts of this plant species were subjected to hydrodistillation to obtain an essential oil. A total of 93 compounds were identified with 2,3,6-trimethyl benzaldehyde (19.0%), spathulenol (9.0%), (E)-caryophyllene (5.4%), and caryophyllene oxide (5.4%) as the main components. The biological activities of F. nodosa essential oil were also investigated. This oil showed an interesting antioxidant potential in a 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) test (IC50 of 14.05 µg/mL). Additionally, hypoglycemic and antilipidemic effects were evaluated. Lipase enzyme was inhibited with an IC50 value of 41.99 µg/mL. Obtained data demonstrated that F. nodosa could be considered a promising source of bioactive compounds useful for the treatment and management of obesity.

Ceiba speciosa (A. St.-Hil.) Seeds Oil: Fatty Acids Profiling by GC-MS and NMR and Bioactivity.

This study aimed to evaluate the chemical composition by gas chromatography-mass spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR) analyses, the antioxidant activities evaluated by different in vitro assays namely 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), Ferric Reducing Ability Power (FRAP), and ß-carotene bleaching tests, and the inhibitory effects of enzymes linked to obesity (lipase, α-amylase, and α-glucosidase) of fixed seed oil of Ceiba speciosa (A. St.-Hil.). Fourteen compounds were identified. Linoleic acid (28.22%) was the most abundant followed by palmitic acid (19.56%). Malvalic acid (16.15%), sterculic acid (11.11%), and dihydrosterculic acid (2.74%) were also detected. C. speciosa fixed oil exerted a promising ABTS radicals scavenging activity with an IC50 value of 10.21 µg/mL, whereas an IC50 of 77.44 µg/mL against DPPH+ radicals was found. C. speciosa fixed oil inhibited lipase with an IC50 value of 127.57 µg/mL. The present investigation confirmed the functional properties of C. speciosa fixed oil, and proposes its use as valuable source of bioactive constituents.

Synthesis of Rosmarinic Acid Amides as Antioxidative and Hypoglycemic Agents.

Type 2 diabetes mellitus (T2DM) is an important metabolic disorder for which there is an urgent need for new antidiabetic drugs. α-Glucosidase inhibition is an established protocol for T2DM therapy. Because hyperglycemia causes oxidative tissue damage, the development of agents with both α-glucosidase inhibition and antioxidant activity from natural or natural-derived polyphenols such derivatives of rosmarinic acid (RA) represents an attractive therapeutic option. We report a study on amides 1-10 derived from RA and their evaluation for yeast α-glucosidase inhibition and antioxidant activity (DPPH and ORAC tests). All amides showed higher inhibitory activity than that of RA, were by far more potent than the antidiabetic drug acarbose, and proved to be effective antioxidants. A molecular docking study displayed significant binding interactions of RA amides with the active site of α-glucosidase. This in silico optimization study led to the design and synthesis of amides 9 (IC50 = 42.3 µM) and 10 (IC50 = 35.2 µM), showing the most potent α-glucosidase inhibition and good antioxidative properties. A kinetic study showed that 10 acts as a mixed type inhibitor.

Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement.

Oleanolic and ursolic acids are two ubiquitous isomeric triterpene phytochemicals known for their anticancer activity. A set of derivatives of the two compounds with a modified oxidation state and lipophylicity at C-3 and C-28 positions, were prepared and tested as anticancer agents versus the lines HepG2, Hep3B and HA22T/VGH of hepatocarcinoma, a strongly aggressive tumor that is not responsive toward the standard therapies. New derivatives containing a three carbons side chain on the C-3 position were synthetized in both stereoisomeric forms by the Barbier-Grignard procedure and three of them were found to be active toward all of the three targets. The implication of the transcriptional nuclear factor NF-κB in the mechanism of action was assessed for the more active compounds in the set, as hepatocellular carcinoma (HCC) cyto-types are known to overexpress NF-κB.

A Review of the Phytochemistry, Traditional Uses, and Biological Activities of the Genus Ballota and Otostegia.

The 2 genera Ballota and Otostegia, belonging to the Lamiaceae family, are closely related taxonomically and found mainly in the Mediterranean area, Middle East, and North Africa. Since ancient times, they have been largely employed in traditional medicine for their biological properties such as antimicrobial, anti-inflammatory, antispasmodic, insecticidal, anti-malaria, etc. Phytochemical investigations of Ballota and Otostegia species have revealed that diterpenoids are the main constituents of the genera. A large number of flavonoids and other metabolites were also identified. This review, covering literature from 1911 up to 2018, includes traditional uses, chemical profiles (both of volatile and nonvolatile metabolites), and biological properties of all the taxa of these 2 genera studied to date.

Essential Oil Composition of Alluaudia procera and in Vitro Biological Activity on Two Drug-Resistant Models.

Drug resistance is a major obstacle in antibiotic and antitumor chemotherapy. In response to the necessity to find new therapeutic strategies, plant secondary metabolites including essential oils (EOs) may represent one of the best sources. EOs in plants act as constitutive defenses against biotic and abiotic stress, and they play an important role in the pharmacology for their low toxicity, good pharmacokinetic and multitarget activity. In this context, natural products such as EOs are one of the most important sources of drugs used in pharmaceutical therapeutics. The aim of this paper was to identify the chemical composition of the essential oil of Alluaudia procera leaves, obtained by hydrodistillation and analysed by gas chromatography-mass spectrometry, and to verify its biological activities on acute myeloid leukemia cancer cell HL60 and its multidrugresistant variant HL60R and the Gram-positive Staphylococcus aureus exhibiting multi-antibiotic resistance. We speculate that cytotoxic and antibiotic effects observed in the tested resistant models may be due to the coordinate activities of forty compounds detected or to the C16 macrocyclic lactones which are the major ones (30%). Our data confirm the possibility of using EOs as therapeutic strategies in resistant models is due to the heterogeneous composition of the oils themselves.

Bioactive Constituents of Juniperus turbinata Guss. from La Maddalena Archipelago.

A comprehensive phytochemical study of Juniperus turbinata (Cupressaceae) collected from La Maddalena Archipelago (Sardinia, Italy) is reported. Both the essential oil and the ethanolic extract obtained from the aerial parts were analyzed. The essential oil appears to belong to a new chemotype compared to other Mediterranean juniper accessions, as it was favored by geographic isolation of the isles. It showed a low content of monoterpene hydrocarbons and α-terpineol, ent-manoyl oxide, 1,10-di-epi-cubenol as the major constituents. The ethanolic fraction contained mainly diterpenoids. Among these, 15-formyloxyimbricatolic acid (7) is a new natural product since it has hitherto been obtained only by synthetic route. The phenolic fraction contained biflavonoids: cupressuflavone (9), followed by minor amounts of amentoflavone (10) and hinokiflavone (11). The essential oil and six purified compounds (1 - 4, 8 and 9) were assessed for biological activities, namely antioxidant (assessed by DPPH· , ABTS·+ and FRAP methods) and cytotoxic effects towards selected human tumor cell lines (MDA-MB 231, A375 and HCT116 cells). Compound 3 exhibited higher radical scavenging activity against ABTS·+ radical than the reference Trolox. Noteworthy, compound 8 showed powerful effects towards tumor cell lines, with IC50 values in the range of 0.060 - 0.201 µm, which make it a promising anticancer drug candidate.

Chemodiversity of the Essential Oil from Leaves of Abies nebrodensis (Lojac.) Mattei.

Abies nebrodensis (Lojac.) Mattei (Pinaceae) is a species occurring in a very small population only in a restricted area of Sicily. Its taxonomic classification as different species has been object of discussion. In this work the chemical composition of the essential oil from the leaves is presented for the first time and compared to the essential oils from other euroasiatic species reported in literature. Peculiar characteristics of the essential oil of A. nebrodensis are highlighted.

Powerful tumor cell growth-inhibiting activity of a synthetic derivative of atractyligenin: involvement of PI3K/Akt pathway and thioredoxin system.

BACKGROUND: The semi-synthetic ent-kaurane 15-ketoatractyligenin methyl ester (SC2017) has been previously reported to possess high antiproliferative activity against several solid tumor-derived cell lines. Our study was aimed at investigating SC2017 tumor growth-inhibiting activity and the underlying mechanisms in Jurkat cells (T-cell leukemia) and xenograft tumor models. METHODS: Cell viability was evaluated by MTT assay. Cell cycle progression, reactive oxygen species (ROS) elevation and apoptotic hallmarks were monitored by flow cytometry. Inhibition of thioredoxin reductase (TrxR) by biochemical assays. Levels and/or activation status of signaling proteins were assessed by western blotting. Xenograft tumors were generated with HCT 116 colon carcinoma cells. RESULTS: SC2017 displayed cell growth-inhibiting activity against Jurkat cells (half maximal inhibitory concentration values (IC50)<2µM), but low cell-killing potential in human peripheral blood mononuclear cells (PBMC). The primary response of Jurkat cells to SC2017 was an arrest in G2 phase followed by caspase-dependent apoptosis. Inhibition of PI3K/Akt pathway and TrxR activity by SC2017 was demonstrated by biochemical and pharmacological approaches. At least, SC2017 was found to inhibit xenograft tumor growth. CONCLUSIONS: Our results demonstrate that SC2017 inhibits tumor cell growth in in vitro and in vivo models, but displays moderate toxicity against PBMC. We also demonstrate that SC2017 promotes caspase-dependent apoptosis in Jurkat cells by affecting Akt activation status and TrxR functionality. GENERAL SIGNIFICANCE: Our observations suggest the semi-synthetic ent-kaurane SC2017 as a promising chemotherapeutic compound. SC2017 has, indeed, shown to possess tumor growth inhibiting activity and be able to counteract PI3K/Akt and Trx system survival signaling.

Cytotoxic activity and composition of petroleum ether extract from Magydaris tomentosa (Desf.) W. D. J. Koch (Apiaceae).

The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as 7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The antiproliferative activity of Magydaris tomentosa flower extract has been evaluated in vitro on murine monocye/macrophages (J774A.1), human melanoma (A375) and human breast cancer (MCF-7) tumor cell lines, showing a major activity against the latter.

Secondary metabolites from Pinus mugo Turra subsp. mugo growing in the Majella National Park (Central Apennines, Italy).

In this study, we examined the composition regarding secondary metabolites of P. mugo Turra ssp. mugo growing in the protected area of Majella National Park, which is the southernmost station of the habitat of this species. Both the nonpolar and polar fractions were considered. In particular, the essential-oil composition showed a high variety of compounds, and 109 compounds were detected, and 101 were identified, among which abietane-type compounds have a taxonomic relevance. Abietanes were also isolated from the polar fraction, together with an acylated flavonol and a remarkably high amount of shikimic acid.

Phytochemical profile and apoptotic activity of Onopordum cynarocephalum.

A phytochemical investigation of acetone and chloroform extracts of the aerial parts of Onopordum cynarocephalum Boiss. et Blanche was carried out. It led to the isolation of two new sesquiterpenes, the elemane aldehyde (2) and the eudesmane (11), together with 15 known compounds: two lignans (1 and 15) and 13 sesquiterpenes (3-10, 12-14, 16, 17). The structures were elucidated by spectroscopic analyses, especially 1D and 2D NMR spectra. The anti-growth effect against three human melanoma cell lines, M14, A375, and A2058, of the different extracts and compounds of O. cynarocephalum was also investigated. Among them, the chloroform extract exhibited the strongest biological activity, while the most active compounds were the lignan arctigenin (1), and the sesquiterpenes, compounds 3, 5, and 6 belonging to the elemane type, and 7 belonging to the eudesmane type. Our data also demonstrate that acetone and chloroform extracts induce, in the A375 cell line, apoptotic cell death that could be related to an overall action of the compounds present, but in particular to the lignans arctigenin (1) and the sesquiterpenes compounds 3-8 and 16. In fact, these molecules were able to induce a high DNA fragmentation, correlated to a significant increase of the caspase-3 enzyme activity. Furthermore, apoptosis appears to be mediated, at least in part, via PTEN activity and the inhibition of Hsp70 expression.

Flavonoids in subtribe Centaureinae (Cass.) Dumort. (tribe Cardueae, Asteraceae): distribution and (13)C-NMR spectral data.

This review reports the occurrence of flavonoids in subtribe Centaureinae of Asteraceae family. It extensively covers the literature up to 2010 and collects all available (13)C-NMR data.

Cytotoxic effect of eudesmanolides isolated from flowers of Tanacetum vulgare ssp. siculum.

A phytochemical analysis of the dichloromethane extract from the flowers of a subspecies of Tanacetum vulgare growing in Sicily was carried out. Five known sesquiterpene lactones with the eudesmane skeleton have been isolated and the cytotoxic activity of these compounds was tested in vitro on A549 (human lung carcinoma epithelial-like) and V79379A (Chinese hamster lung fibroblast-like) cells using the tetrazolium salt reduction (MTT) assay. All of tested compounds induced high time- and concentration-dependent cytotoxic effects.

Chemical composition of essential oil from Italian populations of Artemisia alba Turra (Asteraceae).

The use of essential oils as chemotaxonomic markers could be useful for the classification of Artemisia species and to caracterize biodiversity in the different populations. An analysis of the chemical composition of four essential oils from Italian populations of Artemisia alba Turra (collected in Sicily, Marche and Abruzzo) was investigated. In this paper an in depth study of the significant differences observed in the composition of these oils is reported.

A study on the essential oil of Ferulago campestris: how much does extraction method influence the oil composition?

The essential oil of different parts of Ferulago campestris (Bess.) collected in Sicily has been extracted by microwave-assisted hydrodistillation (MAHD) and by classic hydrodistillation (HD). A comparative qualitative-quantitative study on the composition of the oils was carried out. A total of 100 compounds were identified in the oils obtained by MAHD, whereas 88 compounds characterized the HD oils. The most prominent components were, in all different parts of F. campestris and in both extraction methods, 2,4,5-trimethylbenzaldehyde and 2,4,6-trimethylbenzaldehyde isomers; the latter was not previously found. The attempt to evaluate where the oil components are located in all parts of the plant was carried out by means of a kinetic study. Then, electron microscopy observation on the different parts before and after MAHD and HD was performed.

The ethnobotany, phytochemistry and biological properties of genus Ferulago - A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Ferulago, belonging to the Apiaceae family, is found mainly in the Mediterranean area, Southwest and Middle Asia, the Caucasus and North Africa. Since ancient times, species of this genus have been largely employed in traditional medicine for their biological properties such as antimicrobial, anti-inflammatory, antispasmodic, insecticidal, and anti-malaria, cholinesterase inhibition effects, etc. AIMS: The scope of this paper is to present a comprehensive respect review of this interesting genus including traditional uses, chemical composition of volatile and non-volatile metabolites, and in vitro and in vivo biological properties either utilizing the crude extracts or essential oils, or the single isolated compounds. Furthermore, critical considerations of the published data have been highlighted by comparing them with the results obtained from species of other genus belonging to the Apiaceae family. MATERIALS AND METHODS: The available information on these genera was collected from scientific databases and cover from 1967 up to 2020. The following electronic databases were used: PubMed, SciFinder, Science Direct, Scopus, Web of Science and Google Scholar. The search terms used for this review included Ferulago, all the botanical names of the species, both accepted names or synonyms, essential oils, volatile components, traditional uses, activity, pharmacology, and toxicity. No limitations were set for languages. A total of 230 articles were included in the present review. RESULTS: Researches performed on either crude extracts, solvent fractions or isolated pure compounds from species of genus Ferulago showed several biological properties such as antibacterial, antifungal, antioxidant, antidiabetic, enzymatic, cytotoxic, anticancer, hepatoprotective, nephroprotective, antileishmanial, antimalarial, anticoagulant, anti-inflammatory, insecticidal, etc. Activities. Phytochemical investigations of Ferulago species have revealed that coumarins are the main constituents of the genera. A large number of flavonoids, terpenoids and other metabolites were also identified. Furthermore, a complete review on the essential oil composition of all the taxa studied so far has been also included. CONCLUSION: In the present study, we have provided scientific information and research developments on traditional uses, phytochemical profiles, biological activities and industrial practices on the Ferulago genus. The commercial use and the applications in agri-food sector of some of these species have been also considered. In fact, the various extracts and essential oils have been used as antioxidants and/or as antimicrobial agents, for the stabilization of sunflower and soybean oil, for food packagings, as antioxidants of mayonnaise and yogurt during their storage and, also, as economically valid source for obtaining single compounds, more expensive at a synthetic level.

Phytochemical profile and insecticidal activity of Drimia pancration (Asparagaceae) against adults of Stegobium paniceum (Anobiidae).

Chemical and spectroscopic investigation of the bulbs of Drimia pancration resulted in the isolation of one known flavonol (1), never isolated from this plant species, and of three previously described steroidal saponins (2-4), but whose configuration at their stereogenic centres was not clearly determined. By mean of 1H NMR, 13C NMR, nuclear overhauser effects (NOE) and two-dimensional NMR spectra the full stereochemical structures of compounds 2-4 were proved and all the 1H and 13C signals were assigned. Furthermore, the methanol and butanol extracts of D. pancration were tested against adults of Stegobium paniceum beetles. Despite the non-significant results regarding the repellent activity and contact toxicity, promising results were obtained from the feeding tests.