Seseli tortuosum L. subsp. tortuosum Essential Oils and Their Principal Constituents as Anticancer Agents.

Seseli tortuosum L. subsp. tortuosum, belonging to the Apiaceae family, is a species that grows in Europe, mainly in the Mediterranean regions. The history of its application in traditional medicine highlights its various biological properties. Trying to explore the phytochemistry and pharmacological aspects of this species, the essential oils (EOs) extracted from flowers, stems, and roots of a locally wild accession, never previously investigated, growing in Sicily, Italy, were investigated. The chemical composition of all EOs, obtained by the hydrodistillation method, was evaluated by GC-MS. The most abundant class of all investigated samples was that of monoterpene hydrocarbons (79.98-91.21%) with p-cymene, α-pinene, ß-pinene, and ß-ocimene as major compounds. These EOs, and their main components, were tested for their possible anticancer activity. Obtained data provided evidence that among the different EOs tested, at the dose of 100 µg/mL, those extracted from stems and roots were particularly effective, already at 24 h of treatment, in reducing the cell viability of 42% and 95%, respectively, in HCT116 colon cancer cell line. These EOs also exerted a remarkable cytotoxic effect that was accompanied by morphological changes represented by cell shrinkage as well as a reduction in residual cell population. Differently, modest effects were found when EOs extracted from flowers were tested in the same experimental conditions. The evaluation of the phytocompounds mainly represented in the EOs extracted from different parts of the plant and tested in a range of concentrations between 20 and 200 µg/mL, revealed that α-pinene, ß-pinene, and p-cymene exerted only modest effects on cell viability. Differently, a remarkable effect was found when ß-ocimene, the most abundant phytocomponent in EOs from roots, was tested on colon cancer cells. This phytocompound, among those identified in EOs from Seseli tortuosum L. subsp. tortuosum, was found to be the most effective in reducing colon cancer cell viability with IC50 = 64.52 µg/mL at 24 h of treatment. All together, these data suggest that ß-ocimene could be responsible for the effects observed in colon cancer cells.

Phytochemical investigation and antitumor activity of coumarins from Sicilian accession of Ferulago nodosa (L.) Boiss. roots.

Ferulago nodosa (L.) Boiss. (Apiaceae) is a species occurring in the Balkan-Tyrrhenian area being present in Crete, Greece, Albania, and probably in Macedonia. From the roots of this accession of species, not previously investigated, four coumarins, grandivittin, aegelinol benzoate, felamidin and aegelinol, and two terpenoids, (2E)-3-methyl-4-[(3-methyl-1-oxo-2-buten-1yl)oxy]-2-butenoic acid and pressafonin-A, were isolated and spectroscopically characterized. The last one was never detected in Ferulago species. The evaluation of the anti-tumor effects of F. nodosa coumarins on colon cancer HCT116 cells showed only a modest effect on reduction of tumor cell viability. For aegelinol, the reduction of colon cancer cell viability already appears with 25 µΜ, while using 50 e 100 µM doses of marmesin the residual viability amounted to 70% and 54%, respectively. This effect resulted more evident at higher doses of compounds (at 200 µM from 80% to 0%). The most effective compounds resulted coumarins lacking ester group.

Sambucus nigra L. (fam. Viburnaceae) in Sicily: Distribution, Ecology, Traditional Use and Therapeutic Properties.

Sambucus nigra, the elderberry, has long been used for its medicinal properties in treating numerous diseases. Based on this traditional knowledge, its different pharmacological activities have been the focus of active research. All parts of the tree have long been used in traditional medicine, that is, the bark, the leaves, the flowers and the fruit. This study, carried out in Sicily (Italy), concerns the traditional uses of elder against human diseases. In order to trace the history of man's interaction with elder on the island, multidisciplinary research was carried out, aiming at (1) presenting a comprehensive overview of elderberry's applications and activities and (2) bridging traditional knowledge (uses and beliefs) with modern science, i.e., the most recent scientific findings in the biomedical and pharmacological fields. A rigorous literature review of scientific (and other local) reports on the elderberry tree and its application in food, health and household applications was undertaken. This article also provides a synthetic and updated picture of the ecology and distribution of S. nigra in Sicily. The elderberry is quite widespread in Sicily, yet its distribution is discontinuous. It prefers hedges, riparian woodlands, forest margins and clearings and is rather common along the watercourses flowing in the canyons of the Hyblaean Plateau, in the Madonie Mts. and in Enna province. Indeed, many old plants are often found near sacred places and rural houses, suggesting that in the past, it was extensively planted on purpose for its multiple uses. The complementary data obtained from multidisciplinary research confirm the usefulness of this approach in building a comprehensive and correct picture of the distribution of the most common woody species, for which the available knowledge is often fragmentary and imprecise.

Seseli bocconei Guss. and S. tortuosum subsp. maritimum Guss. essential oils inhibit colon cancer cell viability.

In this study, the chemical compositions of two essential oils (EOs) obtained from different parts (flowers, leaves, stems, and roots) of Seseli bocconei Guss. and of Seseli tortuosum subsp. maritimum Guss., wild endemic species of Sicily, were investigated. The main classes of metabolites for the essential oils of S. bocconei were, respectively, monoterpenes hydrocarbons for flowers, sesquiterpenes hydrocarbons for leaves, and a breakdown between the two previously mentioned classes for stems. In the case of S. tortuosum subsp. maritimum, on the other hand, the main metabolite class for all the vegetative parts analyzed (flowers, stems, and roots) was monoterpene hydrocarbons, with a slight percentage in other non-terpenoid compounds. Furthermore, the EOs' antitumor effects against HCT116, human colon cancer cells were evaluated. Cell viability assays evidenced that stems' EOs of both plants exhibit strong cytotoxic effects at low concentrations, while the EOs from other vegetative parts do not show a relevant effect. In fact, EO of stems of S. tortuosum subsp. maritimum reduced the cell viability of 82% at the concentration of 125 µg/mL, while at the concentration of 250 µg/mL of stems EO of S. bocconei the 97% of cells resulted dead. The analysis of the effects exerted by the main phytocostituents (S-(-)-limonene, R-(+)-limonene, sabinene, (1S)-(-)-α-pinene, (1R)-(+)-α-pinene, and (-)-ß-pinene, and germacrene D) of these EOs on colon cancer cells revealed germacrene D as a new promising molecule with anticancer properties that deserve to be explored in future directions.

Essential oil of Foeniculum vulgare subsp. piperitum fruits exerts an anti­tumor effect in triple­negative breast cancer cells.

At present, the growing spread of tumor cases worldwide renders the research of new promising and selective anticancer drugs urgent. The biological action of extracts of medicinal plants or their essential oils (EOs) is an emerging field of interest, since they could comprise a rich source of phytochemicals that can prove promising. In the present study, the biological activity and mechanism of action of the EO of Foeniculum vulgare subsp. piperitum fruits (FVPEO) were investigated using MTT assays, morphological analyses and western blotting in MDA­MB231 cells, a triple­negative breast cancer cell line. The findings revealed that FVPEO could exert strong anticancer effects, causing a dose­dependent inhibition of breast cancer MDA­MB231 cell growth, accompanied with DNA condensation and fragmentation. The cytotoxic effect of FVPEO was counteracted by the addition of the antioxidant N­acetylcysteine and was associated with a marked increase in reactive oxygen species and stress­related proteins; such as manganese superoxide dismutase, c­Jun, phospho­c­Jun N­terminal kinase and nuclear factor E2­related factor 2, and the latter's transcriptional targets, Heme oxygenase­1 and NAD(P)H quinone oxidoreductase 1 (NQO1). As evidenced by the activation of caspase­3 and fragmentation of poly(ADP­ribose) polymerase­1, which are typical apoptosis markers, FVPEO promoted apoptotic cell death accompanied with an increase in phosphorylated H2A histone family member X and the activation of the NQO1/p53 axis. In combination, the present experiments provided evidence that FVPEO could represent a reservoir of biologically active compounds suitable for both cancer prevention and treatment.

Phytochemical investigation of the needles of Abies nebrodensis (Lojac.) Mattei.

Abies nebrodensis (Lojac.) Mattei (Pinaceae) is a species living in a very small population only in a confined area of Sicily. In this study, the dichloromethane extract of the leaves was analyzed. Apart from three already known metabolites namely dehydroabietic acid; maltol; and rheosmin, previously detected in other species of Abies, a lanostane derivative was isolated. Its chemical structure was elucidated by means of extensive spectroscopic methods.

Sicilian Litchi Fruit Extracts Induce Autophagy versus Apoptosis Switch in Human Colon Cancer Cells.

Litchi chinensis Sonnerat is a tropical tree whose fruits contain significant amounts of bioactive polyphenols. Litchi cultivation has recently spread in Sicily where the climate conditions are particularly favorable for this crop. Recent findings have shown that Litchi extracts display anti-tumor and pro-apoptotic effects in vitro, but the precise underlying mechanisms have not been fully elucidated. In this study, we report for the first time the effects of Sicilian litchi fruit extracts on colon cancer cells. The results indicated that litchi exocarp, mesocarp and endocarp fractions reduce the viability and clonogenic growth of HT29 cells. These effects were due to cell cycle arrest in the G2/M phase followed by caspase-dependent cell death. Interestingly, litchi exocarp and endocarp triggered a precocious autophagic response (16⁻24 h), which was accompanied by an increase in the level of autophagy related 1/autophagy activating kinase 1 (ATG1/ULK1), beclin-1, microtubule associated protein 1 light chain 3 (LC3)-II and p62 proteins. Autophagy inhibition by bafilomycin A1 or beclin-1 silencing increased cell death, thus suggesting that autophagy was initially triggered as a pro-survival response. Significant effects of Litchi extracts were also observed in other colon cancer cells, including HCT116 and Caco-2 cells. On the other hand, differentiated Caco-2 cells, a model of human enterocytes, appeared to be insensitive to the extracts at the same treatment conditions. High-Performance Liquid Chromatography⁻Electrospray Ionization-Quadrupole-Time-Of-Flight HPLC/ESI/Q-TOF evidenced the presence of some polyphenolic compounds, specifically in exocarp and endocarp extracts, that can account for the observed biological effects. The results obtained suggest a potential therapeutic efficacy of polyphenolic compounds purified from Sicilian Litchi fractions for the treatment of colon cancer. Moreover, our findings indicate that modulation of autophagy can represent a tool to improve the effectiveness of these agents and potentiate the anti-tumor response of colon cancer cells.

Chemical composition, in vitro antitumor and pro-oxidant activities of Glandora rosmarinifolia (Boraginaceae) essential oil.

The biological properties of essential oils have been demonstrated in the treatment of several diseases and to enhance the bioavailability of other drugs. In natural habitats the essential oils compounds may play important roles in the protection of the plants as antibacterials, antivirals, antifungals, insecticides and also against herbivores by reducing their appetite for such plants or by repelling undesirable others. We analyzed by gas-chromatography mass spectrometry the chemical composition of the essential oil of aerial parts of Glandora rosmarinifolia (Ten.) D.C. Thomas obtained by hydrodistillation and verified some biological activities on a panel of hepatocellular carcinoma cell lines (HA22T/VGH, HepG2, Hep3B) and triple negative breast cancer cell lines (SUM 149, MDA-MB-231). In the essential oil we detected 35 compounds. The results of the biological assays indicate that essential oil of G. rosmarinifolia induces cell growth inhibition at concentration-dependent way in all cell line models. This oil does not seem to possess antioxidant activity, while the cytotoxicity of G. rosmarinifolia essential oil appeared to involve, at least in part, a pro-oxidant mechanism. Our results show for the first time the antitumoral and pro-oxidant activities of G. rosmarinifolia essential oil and suggest that it may represent a resource of pharmacologically active compounds.

Chemical composition and antimicrobial activity of the essential oils of some species of Anthemis sect. Anthemis (Asteraceae) from Sicily.

The chemical composition of the essential oils isolated from the aerial parts of Anthemis arvensis L. subsp. arvensis, Anthemis cretica subsp. messanensis (Brullo) Giardina & Raimondo and from flowers and leaves of Anthemis cretica subsp. columnae (Ten.) Frezén were determinated by GC-FID and GC-MS analyses. Torreyol (85.4%) was recognised as the main constituent of the Anthemis arvensis subsp. arvensis essential oil, while in the essential oils of Anthemis cretica subsp. messanensis, collected on the rock and cultivated in Hortus Botanicus Panormitanus, (E)-chrysanthenyl acetate (28.8 and 24.2% resp.), 14-hydroxy-α-humulene (8.1 and 5.3% resp.), santolina triene (8 and 5.8% resp.) and α-pinene (6.7 and 5.4% resp.) prevailed. 18-cineole (13.3 and 12.2% resp.), was the main component of both flower and leaf oils of Anthemis cretica subsp. columnae together with δ-cadinene (9.0 and 8.2% resp.) and (E)-caryophyllene (8.3 and 5.6% resp.).

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.

Essential Oils and Pure Volatile Compounds as Potential Drugs in Alzheimer's Disease Therapy: An Updated Review of the Literature.

BACKGROUND: The use of aromatic plants to relief different illness is not a new therapy. Actually aromatic plants have been used for many centuries by different cultures around the world. Pharmacological studies provide scientific support to the traditional use of aromatic medicinal plants and aromatherapy; nevertheless, more clinical trials are required regarding to their effectiveness in order to establish a guidance for their use in routine healthcare. Moreover, modern medicine in studies about olfactory function has attained great achievements and got Nobel Prize in 2004. These new searches have obviously fueled interest in the essential oils and volatile compounds of natural origin. Several reviews on the newly discovered AChEi obtained from plants, fungus and marine organisms have also been published over the last years. The majority of these AChEi belong to the alkaloid group, including indole, isoquinoline, quinolizidine, piperidine and steroidal alkaloids. RESULTS: Probably the interest in the essential oils and volatile compounds will be fueled from the new available scientific data about receptor on olfactory mucosa of nasal cavity. It can receive and distinguish different odor molecules, which produce nerve impulse and transmit into olfactory bulb via olfactory nerves. The nerve cells in the olfactory bulb transmit the signals into hippocampus. Because hippocampus is closely related with learning and memory functions, the volatile compounds can be potential drugs in AD therapies.

Chemical composition of volatile and fixed oils from of Salvia argentea L. (Lamiaceae) growing wild in Sicily.

The chemical compositions of the essential oil and of the non-polar extracts (petroleum ether, dichloromethane) of the aerial parts (flowers, leaves and stems) of Salvia argentea L. were determined by GC-FID and gas chromatography-mass spectrometry analysis. 14-Hydroxy-α-humulene (40.1%) was recognised as the main constituents of the essential oil of S. argentea, together with 1,3,8-p-menthatriene (12.1%), globulol (7.4%) and ß-sesquiphellandrene (5.8%). Tritriacontane (9.9% and 14.1%), heptacosane (8.4% and 10.5%), hentriacontane (8.3% and 10.9%), tetradecanal (8.4% and 10.2%) and methyldotriacontane (7.9% and 7.6%) were recognised as the main constituents of the extracts in petroleum ether and dichloromethane, respectively, whereas methyl linolenate (36.6% and 13.5%) and methyl myristoleate (10.5% and 18.5%) were recognised as the main constituents of the methylated extracts.

Chemical composition of the essential oil of Jacobaea maritima (L.) Pelser & Meijden and Jacobaea maritima subsp. bicolor (Willd.) B. Nord. & Greuter (Asteraceae) collected wild in Croatia and Sicily, respectively.

In this study, the chemical compositions of the essential oils from aerial parts (JmA) and radices (JmR) of Jacobaea maritima (L.) Pelser & Meijden, collected in Croatia, and of Jacobaea maritima subsp. bicolor (Willd.) B. Nord. & Greuter, collected in Sicily, were evaluated by using gas chromatography and gas chromatography-mass spectrometry. The main components of the essential oil from J. maritima, both in JmA and JmR, were pentacosane (15.7%), heptacosane (13.1%) and nonacosane (8.1%) whereas the essential oil from J. maritima subsp. bicolor was characterised by the presence of hexadecanoic acid (14.6%), caryophyllene oxide (9.3%) and hexahydrofarnesylacetone (6.5%). The comparison of the essential oil with other studied oils of the genus Jacobaea is discussed.

Chemical composition of the essential oil of the local endemics Centaurea davidovii and C. parilica (Asteraceae, sect. Lepteranthus) from Bulgaria.

In the present study the chemical compositions of the essential oils from aerial parts of Centaurea davidovii Urum. and C. parilica Stoj. & Stef., both endemic to Bulgaria, were evaluated by GC and GC-MS. The main components of C. davidovii were ß-eudesmol (13.9%), spathulenol (13.3%), caryophyllene oxide (10.1%) and (Z)-phytol (5.4%). The main components of Cparilica were hexadecanoic acid (39.2%), (Z,Z)-9,12-octadecadienoic acid (11.9%), caryophyllene oxide (6.8%) and spathulenol (6.6%). In order to compare the essential oils composition of these taxa and of related species a PCA analysis was carried out.

Chemical composition, antimicrobial and antioxidant activity of the essential oils from Pimpinellatragium Vill. subsp. glauca (C. Presl.) C. Brullo & Brullo (Apiaceae) growing wild in Sicily.

The essential oils from flowers, leaves and stems hydrodistilled from Pimpinella tragium Vill, subsp. glauca were characterised by GC and gas chromatography-mass spectrometry analysis. The C-12 nor-sesquiterpenes are the principal class of metabolites (56.6-70.6%) among which geijerene (28.9÷49.3%) and pregeijerene (10÷19.1%) predominate. Antimicrobial and antioxidant activities were evaluated. The minimum inhibitory concentration values indicate that oil obtained from the stems is the most active for antimicrobial activities and the sample with the biggest antioxidant capacity is the flower oil.

Essential oils of Chiliadenus lopadusanus (Asteraceae).

The essential oils from the leaves and flowers of Chiliadenus lopadusanus growing on Lampedusa Island were obtained by hydrodistillation and analyzed by GC-MS. The major component was camphor (39.4% in the leaves and 24.0% in the flowers), followed in the leaves by torreyol (6.7%), t-cadinol (5.2%) and 1,8-cineole (3.8%), while in the flowers by t-cadinol (15.2%), t-muurolol (5.1%) and torreyol (4.5%). Among the compounds identified, several seem to play a role in antibacterial, antifungal, allelopathic and spasmolytic activity. In addition, several compounds identified in this study seem to influence the attraction of Megachile (Eutricharaea) apicalis (Megachilidae) and Halictus (Seladonia) gemmeus (Halictidae), two hymenopteran here identified as pollinators of Chiliadenus lopadusanus.

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

Asteraceae Bercht. & J. Presl is one of the biggest and most economically important plant families. The taxonomy and phylogeny of Asteraceae is rather complex and according to the latest and most reliable taxonomic classification of Panero & Funk, based on the analysis of nine chloroplast regions, the family is divided into 12 subfamilies and 35 tribes. One of the largest tribes of Asteraceae is Cardueae Cass. with four subtribes (Carlininae, Echinopinae, Carduinae and Centaureinae) and more than 2500 species. Susanna & Garcia-Jacas have organized the genera of Centaureinae (about 800 species) into seven informal groups, which recent molecular studies have confirmed: 1. Basal genera; 2. Volutaria group; 3. Rhaponticum group; 4. Serratula group; 5. Carthamus group; 6. Crocodylium group; 7. Centaurea group. This review summarizes reports on sesquiterpenoids from the Centaureinae subtribe of the Asteraceae family, as well as the (13)C NMR spectral data described in the literature. It further reviews studies concerning the biological activities of these metabolites. For this work, literature data on sesquiterpenes from the Centaureinae subtribe were retrieved with the help of the SciFinder database and other similar data banks. All entries from 1958 until the end of 2011 were considered. This review is addressed to scientists working in the metabolomics field such as chemists, botanists, etc., the spectroscopic data reported make this work a good tool for structural elucidation, the biological section gives useful information to those who wish to study the structure activity relationships.

Metabolites from the aerial parts of the Sicilian population of Artemisia alba.

Phytochemical investigation of the CH2Cl2 extract of the aerial parts of Artemisia alba Turra afforded one new irregular sesquiterpenoid, artemiric acid, and five known metabolites: hydroxydavanone, the coumarins isofraxidin and scopoletin, (6S*, 7S*,10R*)-6,10 -dimethyl-7,10-epoxyocta-11-enoic acid and artalbic acid. From the MeOH extract three flavonoids were identified: chrysoeriol, quercetin and isorhamnetin. The possible biogenetic pathways of artemiric and artalbic acids are discussed.

Monoterpene derivatives from the flowers of Ferulago campestris, (Apiaceae).

Ferulago campestris (Besser) Grec., (Ferula galbanifera (Mill) Kock. = F. campestris), finocchiazzo, is an annual or perennial herb of the Mediterranean area. In this paper the phytochemical studies of the CH2Cl2 and MeOH extracts of the flowers are described. Several ferulol derivatives and a new 10-hydroxy-verbenone ester (7) were isolated. The structure of the new compound was established by extensive NMR analysis, including HMBC and HSQC pulse sequences.

Chemical composition and free radical scavenging activity of the essential oil of Achillea ligustica growing wild in Lipari (Aeolian Islands, Sicily).

In the present study the chemical composition of the essential oils from aerial parts and flowers of Achillea ligustica All., collected in Lipari (Aeolian Islands) was evaluated by GC and GC-MS. (Z)-Chrysanthenyl acetate was the most abundant component of both oils (29.6% in A1 and 27.8% in F1), followed by viridiflorol (16.8% in A1 and 21.6% in F1), bornyl acetate (8.7% in A1 and 11.6% in F1) and 1,8-cineole (7.4% in A1 and 9.3% in F1). A comparison was made of the composition of the different populations studied so far. Futhermore, the free radical scavenging activity of the oil was determined by DPPH and ABTS methods.