Cladanthus scariosus Essential Oil and Its Principal Constituents with Cytotoxic Effects on Human Tumor Cell Lines.

Cladanthus is a small genus of the Asteraceae family comprising just five species that, apart from Cladanthus mixtus (L.) Chevall., has a large distribution in all the Mediterranean countries, mainly in the North Africa area. Several ethnopharmacological uses have been reported for species of this genus. Notably, Cladanthus scariosus (Ball) Oberpr. & Vogt is endemic to Morocco. Seeking to delve deeper into the phytochemistry and pharmacological aspects of this species, in this work, we investigated the essential oil (EO) obtained from the aerial parts of a locally sourced accession, hitherto unexplored, growing wild near Tizi n'Ticha, Morocco. The chemical composition of the EO, obtained by the hydrodistillation method, was evaluated by GC and GC-MS. The most abundant EO constituent was germacrene D (13.2%), the principal representative of the sesquiterpene hydrocarbons class (27.2%). However, the major class of constituents was monoterpene hydrocarbons (43.0%), with α-pinene (11.9%), sabinene (10.2%), p-cymene (8.5%), and α-phellandrene (5.2%) as the most abundant. The EO and its main constituents have been tested for their possible cytotoxic activity against three human tumor cell lines (MDA-MB 231, A375, and CaCo2) using the MTT assay, with corresponding IC50 values of 13.69, 13.21, and 22.71 µg/mL, respectively. Germacrene D and terpinen-4-ol were found to be the most active constituents with IC50 values between 3.21 and 9.53 µg/mL. The results demonstrate remarkable cytotoxic activity against the three human tumor cell lines studied, and in the future, further analyses could demonstrate the excellent potential of C. scariosus EO as an antitumor agent.

Stachys durandiana Coss., an endemic plant of Morocco: chemical composition of its aerial parts essential oil.

The genus Stachys L. (Lamiaceae) comprises more than 300 species as annual or perennial herbs or small shrubs, spread in temperate regions of Mediterranean, Asia, America, and Southern Africa and several species have been used in the traditional medicine of many countries. Section Stachys, one of nineteen sections of genus Stachys, is divided in two subsections: Sylvaticae and Circinatae. In the present study the chemical composition of the essential oil from aerial parts of Stachys durandiana Coss., endemic of Morocco, and belonging to subsection Circinatae, was analysed by GC-MS. No report has been previously published on this species. The result showed the presence of large quantity of monoterpene hydrocarbons (73.3%), being α-pinene (38.0%) ß-pinene (14.8%), and limonene (11.1%) the principal constituents. Furthermore, a complete review on the chemical composition and biological properties of all the other Stachys taxa, belonging to section Stachys, studied so far, was carried out.

Chemical Profile and Healthy Properties of Sicilian Diplotaxis harra subsp. crassifolia (Raf.) Maire.

This study was aimed at investigating the phytochemical profile and bioactivity of Diplotaxis harra subsp. crassifolia (Brassicaceae), a species from central-southern Sicily (Italy), where it is consumed as a salad. For this purpose, LC-ESI/HRMSn analysis of the ethanolic extract was performed, highlighting the occurrence, along with flavonoids, hydroxycinnamic acid derivatives, and oxylipins, of sulfated secondary metabolites, including glucosinolates and various sulfooxy derivatives (e.g., C13 nor-isoprenoids, hydroxyphenyl, and hydroxybenzoic acid derivatives), most of which were never reported before in the Brassicaeae family or in the Diplotaxis genus. Following ethnomedicinal information regarding this species used for the treatment of various pathologies such as diabetes and hypercholesterolemia, D. harra ethanolic extract was evaluated for its antioxidant potential using different in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), Ferric Reducing Ability Power, and ß-carotene bleaching tests. The inhibitory activity of carbohydrate-hydrolyzing enzymes (α-amylase and α-glucosidase) and pancreatic lipase was also assessed. In the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid assay, an IC50 value comparable to the positive control ascorbic acid (2.87 vs. 1.70 µg/mL, respectively) was obtained. The wild-wall rocket salad extract showed a significant α-amylase inhibitory effect. Obtained results indicate that Sicilian wild-wall rocket contains phytochemicals that can prevent hyperglycemia, hyperlipidemia, and obesity.

The essential oil chemical composition of a sicilian (Italy) accession of Doronicum caucasicum M. Bieb.

Doronicum is a relatively small genus belonging to the tribe Senecioneae (Fam. Asteraceae), distributed in Asia, Europe, and North Africa. Some of its species are considered toxic due to the presence of pyrrolizidine alkaloids whereas some other ones are largely utilised in the ethnopharmacology of several countries. In the present study, the essential oil composition of a Sicilian accession of Doronicum caucasicum M. Bieb (syn. D. orientale Hoffm.), not previously investigated, is particularly rich in sesquiterpene hydrocarbons (80.3%) with germacrene D (58.9%), α-humulene (8.8%), and ß-caryophyllene (6.5%) as main metabolites. A comparison with all the essential oils from Doronicum taxa studied so far has been carried out.

The chemical composition of the aerial parts' essential oil of Limonium lobatum (L.f.) Chaz. growing wild in Algeria.

The Limonium genus (Plumbaginaceae) includes several species of perennial herbs and shrubs belonging to a particular type of halophytes, known as 'recretohalophytes'. Limonium species are widely distributed in the Mediterranean region, mainly in the North-Eastern and Southern countries and several bioactivities have been well documented. In the present study, the chemical composition of the essential oil (EO) of the aerial parts of Limonium lobatum (L.f.) Chaz., a species never chemically previously studied and collected in Algeria, which grows in South Spain, North Africa, and SW Asia, was analysed using GC-MS. The main constituents of the EO were monoterpenes involving eucalyptol (14.21%), ß-pinene (8.62%), ß-myrcene (8.18%). Among the sesquiterpene compounds ß-caryophyllene (8.94%) was the major one. The chemical profile of the EO presented here was compared with the EOs of previously investigated Limonium taxa. Furthermore, a complete literature review on the ethno-pharmacological uses of Limonium species was performed.

Synthetic Derivatives of Natural ent-Kaurane Atractyligenin Disclose Anticancer Properties in Colon Cancer Cells, Triggering Apoptotic Cell Demise.

The antitumor activity of different ent-kaurane diterpenes has been extensively studied. Several investigations have demonstrated the excellent antitumor activity of synthetic derivatives of the diterpene atractyligenin. In this research, a series of new synthetic amides and their 15,19-di-oxo analogues obtained from atractyligenin by modifying the C-2, C-15, and C-19 positions were designed in order to dispose of a set of derivatives with different substitutions at the amidic nitrogen. Using different concentrations of the obtained compounds (10-300 µM) a reduction in cell viability of HCT116 colon cancer cells was observed at 48 h of treatment. All the di-oxidized compounds were more effective than their alcoholic precursors. The di-oxidized compounds had already reduced the viability of two colon cancer cells (HCT116 and Caco-2) at 24 h when used at low doses (2.5-15 µM), while they turned out to be poorly effective in differentiated Caco-2 cells, a model of polarized enterocytes. The data reported here provide evidence that di-oxidized compounds induced apoptotic cell death, as demonstrated by the appearance of condensed and fragmented DNA in treated cells, as well as the activation of caspase-3 and fragmentation of its target PARP-1.

Phytochemical Characterization, Antioxidant, and Anti-Proliferative Activities of Wild and Cultivated Nigella damascena Species Collected in Sicily (Italy).

The use of Nigella damascena seeds in the culinary field or as aerial parts infusions in the pharmaceutical and cosmetic fields is widely reported. The biological activity of this plant, as demonstrated over the years, is closely related to its phytochemical content. This investigation focused on the comparative study of the same plants of N. damascena, one totally wild (WND), while the other two, one with white flowers (CWND) and the other with blue flowers (CBND), were subject to cultivation, irrigation, and manual weeding. Using the potential of 1D and 2D-NMR spectroscopy, coupled with MS/MS spectrometric studies, the three methanolic extracts of N. damascena were investigated. Chemical studies have highlighted the presence of triterpene saponin compounds and various glycosylated flavonoids. Finally, the in vitro antiproliferative and antioxidant activities of the three individual extracts were evaluated. The antiproliferative activity performed on U-937, HL-60, and MCF-7 tumor cell lines highlighted a greater anticancer effect of the CBND and CWND extracts compared to the data obtained using WND. The antioxidant activity, however, performed to quantify ROS generation is comparable among the extracts used.

The essential oil composition of Phlomis bovei subsp. maroccana Maire, an endemic species of Morocco.

Phlomis L. is a genus belonging to the Lamiaceae family, distributed in Macaronesia, the Mediterranean basin, Northeast Africa, Central Asia, and Western Himalaya. Plants of this genus are used against various diseases in the ethno-medicine of several countries and some of them are also utilised for culinary purposes. In the present study, the essential oil chemical composition of the aerial parts of Phlomis bovei subsp. maroccana Maire, an endemic species of Morocco, was analysed by GC-MS. No previous paper has been previously published on this taxon. Main constituents of the essential oil were sesquiterpene hydrocarbons (44.48%) with curcumene (11.20%), a very rare compound in Phlomis essential oils, ß-himachalene (6.22%), and ß-cedrene (3.81%) as principal metabolites. 1-hexadecanol (7.75%) and 1-octadecanol (5.32%) were the main constituents among the alcohols (19.66%). A comparison with all the other essential oils from Phlomis taxa has been carried out.

The chemical composition of the aerial parts' essential oil of matthiola fruticulosa (L.) maire growing in Sicily, Italy.

Matthiola Aiton is a genus belonging to the Brassicaceae family, distributed in Macaronesia, the Mediterranean basin, and the Saharo-Sindian region. Plants of this genus are used against various diseases in the ethno-medicine of several countries and a complete review of their usage has been carried out in this paper. In the present study, the essential oil chemical composition of the aerial parts of the Sicilian accession of Matthiola fruticulosa (L.) Maire, a species growing in South-Western Europe, Northern Africa, and Western Asia, was analysed by GC and GC-MS. No previous paper has been previously published on the essential oil of this species. Main constituents of the oil were sulphur compounds (45.5%) with the two quite rare cis and trans isomers of 5-(methylthio)-4-pentenenitrile as principal metabolites (16.3% and 10.7%, respectively). Principal compound of the oil was the diterpene phytol (16.5%) whereas other terpenoids were less abundant (10.6%).

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.

The Biological Properties of the Essential Oil from the Jordan Accession of Phagnalon sinaicum Bornm. & Kneuck.

The genus Phagnalon Cass. (Asteraceae) is composed of widely distributed species and most of them, due to the medicinal properties they possess, are widely used in folk medicine but also as spices in the culinary field. The polar and non-polar extracts, as well as the complex mixtures of their essential oils, from several Phagnalon species and ssp., have shown antibiotic, antiviral, cytotoxic, and several other biological properties. In this work, the chemical composition and the antimicrobial, cytotoxic, and antioxidant properties of the Jordan accession of Phagnalon sinaicum Bornm. & Kneuck. essential oil (EO), an extremely rare plant that grows in ravines in the Middle East, were investigated. The EO, analyzed by GC-MS, was found to be rich in terpenoid compounds, and, in particular, in oxygenated monoterpenes, with the main compound being artemisia ketone (22.3%), followed by α-thujone (17.7%), and santolin alcohol (14.8%). The EO had good antimicrobial activity, especially against Escherichia coli Gram-negative bacterium (3 mg/mL MIC values) and was also effective in counteracting in vitro biofilm formation. Furthermore, this EO showed low cytotoxicity against immortalized human keratinocytes lines, but had good antioxidant activity on the same eukaryotic cellular models.

The chemical composition of the aerial parts' essential oil of Geocaryum capillifolium (Guss.) Coss growing in Sicily (Italy).

The three genera Geocaryum Coss., Conopodium W.D.J. Koch, and Bunium L. are closely related, and their correct identification is complex. The first two genera are distributed in Europe and North Africa, while several Bunium species also occur in Asia. In the present study, we analysed the chemical composition of the essential oil of the aerial parts of Geocaryum capillifolium (Guss.) Coss. a rare species collected in Sicily, which also grows in the Iberian Peninsula, Algeria, and Greece, was analysed using GC-MS. The main constituents of the essential oil were sesquiterpene hydrocarbons involving cis-ß-farnesene (31.2%), trans-ß-caryophyllene (20.0%), and germacrene D (8.5%). The chemical profile of the essential oil presented here was compared with the oils of previously investigated Geocaryum, Conopodium, and Bunium taxa, as reported in the literature. To the best of our knowledge, no report has been previously published about the essential oil of the Sicilian accession of this species.

The chemical composition of the essential oils of two Mediterranean species of Convolvulaceae: Convolvulus althaeoides subsp. tenuissimus collected in Sicily (Italy) and Calystegia silvatica collected in Algeria.

Convolvulus L. and Calystegia R.Br. are two closely related genera of the Convolvulaceae family distributed in Asia, Mediterranean, Macaronesia, East Africa, and Arabia, including about 210 and 30 accepted species, respectively, of flowering plants, present as trees, shrubs, and herbs. The ethnomedical use of Convolvulus species dates to 1730s as they displayed profuse medicinal properties. In the present study, the not previously investigated chemical compositions of the essential oils from aerial parts of Convolvulus althaeoides subsp. tenuissimus (Sm.) Bat., collected in Sicily, and Calystegia sylvatica (Kit.) Griseb., collected in Algeria, were evaluated by GC-MS. The main components of the essential oil of the first one were ß-caryophyllene (28.68%), γ-muurolene (23.75%), and γ-elemene (17.55%), whereas the C. silvatica essential oil was shown to be rich of valeranone (10.77%), viridiflorol (9.45%), and germacrene D (8.61%). Furthermore, a complete literature review on the ethno-pharmacological uses of Convolvulus and Calystegia species was performed.

The chemical composition of the aerial parts essential oils of four Andryala species (Asteraceae) growing wild in Morocco.

Andryala (Asteraceae: Cichorieae) is a little-known Mediterranean-Macaronesian genus whose taxonomy is very much in need of revision. In the present study, the chemical composition of the essential oils (EOs) from aerial parts of as many Andryala species, A. integrifolia, A. cossyrensis, and A. rothia, never studied before, and of A. pinnatifida subsp. mogadorensis, all collected in Morocco, was evaluated by GC-MS. The main components of the EOs of A. integrifolia and A. pinnatifida subsp. mogadorensis were organic acid compounds (41.10% and 43.52%, respectively), whereas A. cossyrensis, and A. rothia were shown to be rich in alkane derivatives (43.10% and 34.29%, respectively). Aldehydic compounds were the second class of metabolites in A. integrifolia and A. rothia (26.67% and 21.91%, respectively), whereas terpenoids, represented in all the four species in limited amounts, were more abundant only in A. pinnatifida subsp. mogadorensis (9.90%) and A. rothia (11.79%) species.

The chemical composition of the aerial parts' essential oil of Cynoglossum clandestinum Desf. growing in Sicily, Italy.

Cynoglossum L. is a taxonomically difficult genus belonging to the Boraginaceae family, distributed in Asia, Europe, mainly in Turkey, and in the Mediterranean region. Plants of this genus are used against various diseases in the ethnomedicine of several countries. In the present study, the chemical composition of the essential oil was obtained from the hydrodistillation of aerial parts of the Sicilian accession of Cynoglossum clandestinum Desf. was analysed by GC and GC-MS. The main constituents of the essential oil were aldehydes and ketones (69.9%) with nonanal (18.9%), 4-sec-butoxy-2-butanone (18.1%), and 3-methyl-butanal (13.1%) as main metabolites. No one paper has been previously published on the essential oil of this species, and there is a lack of studies also in the near related genera. The aim of this work is in fact, to study a species that has never been investigated, and through this, try to help place it within the Boraginaceae family.

Centaurea polyacantha and C. maroccana: the chemical composition of the aerial parts essential oils of these Centaurea species (Asteraceae) collected in Morocco.

In the present study, the chemical composition of the essential oil from the aerial parts of two Centaurea species not previously investigated, C. polyacantha Willd. (sect. Seridia, Asteraceae) and C. maroccana Ball. (sect. Calcitrapa, Asteraceae), collected in Morocco, was evaluated by GC-MS. The main components of the essential oil of the first one were limonene (18.2%), ß-bisabolene (11.5%), (Z)-ß-farnesene (8.6%), and spathulenol (8.3%), whereas the C. maroccana essential oil, practically devoid of terpenoids, was shown to be rich in some unusual Centaurea metabolites: 1-hexadecanol (24.9%), docosane (23.7%), and 1-octadecanol (19.5%). Furthermore, a complete literature review on the composition of the essential oils of all the other taxa of Centaurea, belonging to sections Seridia and Calcitrapa, studied so far, was performed.

Chemical composition, antimicrobial, and antioxidant activities of Opuntia stricta (Haw.) Haw. mucilage collected in Sicily, Italy.

In this work the mucilage obtained from the cladodes of a not previously investigated accession of Opuntia stricta (Haw.) Haw. (syn. Opuntia dillenii (Ker-Gawl) Haw), collected in Sicily, was analysed by 13C-NMR. The yield of mucilage extracted from cladodes in aqueous medium was 2.55%. The monosaccharides identified, after acidic hydrolyses of the mucilage, were arabinose (36.48%), galactose (32.31%), xylose (15.33%), glucose (10.45%) and rhamnose (5.40%). The mucilage showed a sufficient antimicrobial activity and excellent antioxidant property.

Chemical Composition of Salvia fruticosa Mill. Essential Oil and Its Protective Effects on Both Photosynthetic Damage and Oxidative Stress in Conocephalum conicum L. Induced by Environmental Heavy Metal Concentrations.

The genus Salvia L., belonging to the Lamiaceae family, contains more than 900 species distributed in various parts of the world. It is a genus containing aromatic plants used both in the culinary field and above all in the cosmetic area to produce several perfumes. Salvia fruticosa Mill., notoriously known as Greek Salvia, is a plant used since ancient times in traditional medicine, but today cultivated and used in various parts of Europe and Africa. Polar and apolar extracts of this plant confirmed the presence of several metabolites such as abietane and labdane diterpenoids, triterpenoids, steroids, and some flavonoids, causing interesting properties such as sedative, carminative, and antiseptic, while its essential oils (EOs) are mainly characterized by compounds such as 1,8-cineole and camphor. The aim of this work concerns the chemical analysis by GC and GC-MS, and the investigation of the biological properties, of the EO of S. fruticosa plants collected in eastern Sicily. The gas-chromatographic analysis confirmed the presence of 1,8-cineole (17.38%) and camphor (12.81%), but at the same time, also moderate amounts of α-terpineol (6.74%), ß-myrcene (9.07%), camphene (8.66%), ß-pinene (6.55%), and α-pinene (6.45%). To study the protective effect of EOs from S. fruticosa (both the total mixture and the individual compounds) on possible damage induced by heavy metals, an in vitro system was used in which a model organism, the liverwort Conocephalum conicum, was subjected to the effect of a mix of heavy metals (HM) prepared using values of concentrations actually measured in one of the most polluted watercourses of the Campania region, the Regi Lagni. Finally, the antioxidant response and the photosynthetic damage were examined. The exogenous application of the EO yields a resumption of the oxidative stress induced by HM, as demonstrated by the reduction in the Reactive Oxygen Species (ROS) content and by the increased activity of antioxidant enzyme catalase (CAT) and glutathione-S-transferase (GST). Furthermore, plants treated with HMs and EO showed a higher Fv/Fm (maximal quantum efficiency of PSII in the dark) with respect to HMs-only treated ones. These results clearly indicate the protective capacity of the EO of S. fruticosa against oxidative stress, which is achieved at least in part by modulating the redox state through the antioxidant pathway and on photosynthetic damage.

The chemical composition of the aerial parts' essential oil of Nepeta apuleji Ucria (Lamiaceae) growing in Sicily (Italy).

The genus Nepeta L. (Lamiaceae) comprises about 300 species as annual or perennial herbs or small shrubs, spread in central and southern Europe, the Near East, central and southern Asia, and some areas of Africa. Several species have been used in the traditional medicine. In the present study, the chemical composition of the essential oils from aerial parts of two populations of Nepeta apuleji Ucria collected in Sicily, a rare species, growing also in South Spain and NW Africa, were analysed by GC-MS. No one has been previously worked and published on the essential oil of this species. Main constituents of the two oils of the two populations were the monoterpenes ß-pinene (11.6-6.3%) and γ-terpinene (9.4-5.0%), and the sesquiterpenes ß-caryophyllene (11.9-9.8%) and germacrene D (1.8-13.0%). The chemical profile of the two essential oils presented herein and they compared with previously investigated Nepeta taxa oils, reported in the article.