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The search for new bioactive substances with anticancer activity and the understanding of their mechanisms of action are high priorities in the research effort toward more effective cancer treatments. In this article, we analyzed, for the first time, the chemical composition of the essential oil (EO) hydrodistilled from the aerial parts of Vicia ochroleuca Ten. (Leguminosae) by GC–MS. A total of sixteen compounds representing 82.2% of the total composition were identified. The major compounds were phytone (20.11%), hexadecanoic acid (10.23%), 1-octen-3-ol (9.84%), and 10-epi-α-cadinol (7.13%). Additionally, using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method, the EO was tested in vitro against a panel of human cancer cells, including breast (MDA-MB 231), colon (HCT116), melanoma (A375), and glioblastoma (T98G), with corresponding IC50 values of 23.07, 47.05, 51.64, and 64.07 μg/mL, respectively. The results demonstrate cytotoxic activity and suggest that V. ochroleuca EO could be regarded as a natural bioactive source.

In this paper we report the analysis of essential oils from the woods of C. libani and P. pinea and from the berries of J. excelsa. Several differences were observed with respect to previous studie...

The objectives of this study were to evaluate in horse testes the expression of kisspeptin (KiSS) and GnRH1 neuropeptides and their cognate receptors, KiSS1R and GnRH1R, as well as their action on testosterone, GnRH1, prostaglandin F2α (PGF2α), and PGE2 synthesis and cyclooxygenase 1 (COX1) and COX2 activity by Leydig cells in vitro. Testes were obtained from 9 sexually mature horses by surgical castration. Immunohistochemistry, evidenced the presence of KiSS, KiSS1R, GnRH, and GnRH1R in Leydig cells, whereas germinal and Sertoli cells were positive only for GnRH1. Transcripts for both neuropeptides and their cognate receptors were revealed in isolated Leydig cells by RT-PCR. Isolated and purified Leydig cells were in vitro cultured with agonists and antagonists of KiSS (KiSS-10 and KiSS-234, respectively) and GnRH1 (buserelin and antide, respectively). KiSS-10 and buserelin increased (P 0.01) COX1 activity and testosterone and PGF2α basal secretion, while decreased (P 0.01) that of PGE2. KiSS-10 and buserelin did not affect COX2 activity. GnRH1 basal production was increased (P 0.01) by KiSS-10, but not by buserelin. Antide counteracted the KiSS and GnRH1 effects, whereas KiSS-234 influence only those of KiSS. Summarizing, the KiSS/GnRH1 system is present in horse Leydig cells and modulates their endocrine activity. In particular, the endocrine effects of KiSS are mediated by GnRH1, so suggesting that hypothalamic-like interaction between KiSS and GnRH1 occurs also in Leydig cells.

Atractyloside, carboxyatractyloside, their aglycon atractyligenin, and several synthetic derivatives were tested and found to be active against a panel of human tumor cell lines. Atractyligenin was subjected to oxidation, bromination, and elimination reactions, obtaining several compounds. A singular skeleton was synthesized by chemical rearrangement starting from 3 beta-bromo-2,15-diketoatractyligenin methyl ester. The synthesized compounds resulted active against all cell lines tested. In particular, 15-ketoatractyligenin methyl ester and 3 beta bromo-2,15-diketoatractyligenin methyl ester resulted the most active with IC50 values of 0.427 and 0.723 mu M against A375 melanoma cell line. Excellent results were also obtained against the colon cancer cell line CaCo2, with slightly lower antiproliferative activity. An interesting extension of the study should be to analyze the atractyligenin derivatives also as target for human melanoma and human colon cancer cells.

Prangos ferulacea (L.) Lindl. (Fam. Apiaceae), is an orophilous species of eastern Mediterranean and western Asia which possesses several biological properties, which are worthy of exploitation in different fields. With the aim to provide new insights into the phytochemistry and pharmacology of this species, a local accession growing in Sicily (South Italy) was investigated as well. Notably, the P. ferulacea essential oil chemical composition and the antioxidant, anti-acetylcholinesterase (AChE) and cytotoxic activities have been studied. This analysis allowed to identify a new chemotype and to report good biological results for this oil. © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Liriodendron tulipifera L. (Magnoliaceae), also known as "tulip tree," is a hardwood plant native to North America, cultivated all over the world and used on an industrial level, especially for its fine wood and to make honey. It has also been traditionally exploited for its antimalarial properties. However, our knowledge about the bioactivity of its essential oil remains patchy. In this research, we focused on the biological evaluation of the volatile fractions obtained from different parts of the plant which are normally discharged by industry, including leaves, flowers, and fruits. For the purpose, the essential oils were obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Then, they were evaluated as radical scavenging, antioxidant, antimicrobial, and antiproliferative agents by using DPPH, ABTS, FRAP, disk diffusion, and MTT methods, respectively. The significant toxicity exhibited on human tumor cells, namely A375 malignant melanoma, HCT116 colon carcinoma, MDA-MB 231 breast adenocarcinoma, and T98G glioblastoma multiforme cell lines, prompted us to study the mechanism of action by acridine orange/ethidium bromide double staining and caspase 3 assays. Our findings shed light on the potential applications of tulip tree derivatives as anticancer drugs.

Alcohol Use Disorder (AUD) is a chronic disease that develops over the years. The complexity of the neurobiological processes contributing to the emergence of AUD and the neuroadaptive changes occurring during disease progression make it difficult to improve treatments. On the other hand, this complexity offers researchers the possibility to explore new targets. Over years of intense research several molecules were tested in AUD; in most cases, despite promising preclinical data, the clinical efficacy appeared insufficient to justify futher development. A prototypical example is that of corticotropin releasing factor type 1 receptor (CRF1R) antagonists that showed significant effectiveness in animal models of AUD but were largely ineffective in humans. The present article attempts to analyze the most recent venues in the development of new medications in AUD with a focus on the most promising drug targets under current exploration. Moreover, we delineate the importance of using a more integrated translational framework approach to correlate preclinical findings and early clinical data to enhance the probability to validate biological targets of interest.

Prangos ferulacea (L.) Lindl. (Fam. Apiaceae), an orophilous species of eastern Mediterranean and western Asia, possesses a number of biological properties that are worthy of exploitation in different fields. Phytochemical investigations revealed the presence of coumarins, prenyl-coumarins, and furano-coumarins as the main constituents of this species, as well as several flavonoids. Among prenyl-coumarins, osthol is a promising apoptotic agent quite selective toward cancer cells. In addition, the essential oils have been extensively investigated, and several chemotypes have been identified. This work reviews the literature on this species published between 1965 and 2018, describes its volatile and nonvolatile metabolites, and outlines its pharmacological effects.

Pulicaria undulata is used as a traditional herbal remedy in Egypt. We used gas chromatography-mass spectrometry for analysis of essential oil of this plant growing wild in Egypt and 64 compounds were identified. The oil was rich in oxygenated monoterpenes (64.0%) and aromatic derivatives (18.8%). The major components were carvacrol (46.5%), xanthoxylin (18.1%) and carvotanacetone (8.7%). The oil of the Egyptian plant showed significant differences from the oil results reported on this species derived from different accessions. Antioxidant activity was performed by FRAP, DPPH and ABTS assays, and the oil demonstrated a powerful antioxidant properties. Furthermore, cytotoxicity was assessed using MTT assay against three cell lines (A375, T98G, HCT116) and the oil showed moderate results with IC50 of 18.53, 40.64 and 22.23 μg/ml; respectively. The oil showed a good anti-acetylcholinesterase activity (IC50 = 139.2 μg/ml) using Ellman method. In conclusion, the studied oil exhibited a peculiar fingerprint and promising biological activities.

Acmella oleracea (L.) R.K. Jansen, also named jambu, is an edible and medicinal plant native to Brazil but extensively cultivated all over the world due to its diverse utilizations in food, cosmetics, pharmaceutics, and pest management science. Most of applications are related to the presence of active ingredients, namely alkylamides, among which spilanthol is the most important one. On the other hand, the plant biomass resulting from the large-scale cultivation of A. oleracea may yield an essential oil (EO), which can be used for some industrial purposes, for instance as larvicide against vector mosquitoes. This EO is mainly characterized by mono- and sesquiterpenes, however also spilanthol can be detected in the mixture. To maximize the content of spilanthol in the A. oleracea EO, A. oleracea aerial parts obtained from a cultivation in central Italy were subjected to microwave-assisted extraction (MAE). This procedure allowed to obtain a higher yield and spilanthol content when compared with traditional hydrodistillation (0.47 v 0.22 %, and 13.31 vs 2.24 %, respectively). The EO terpene fraction was mainly represented by β-pinene (10.8 %), myrcene (12.3 %), (E)-caryophyllene (19.4 %) and α-humulene (1.1 %). The A. oleracea EO was encapsulated into a nanoemulsion (NE) containing 6 % EO using a high-energy method. The formulation physical stability was assessed by optical microscope and DLS analyses at different timepoints showing stability up to one year of storage. The A. oleracea EO and its NE, along with the isolated spilanthol, were evaluated for acute toxicity against the 3rd instar larvae of Culex quinquefasciatus, a filariasis and arbovirus vector of public health importance, achieving LC50 values of 16.1, 407.5, and 3.1 μL/L, respectively. The larvicidal activity seemed to be not dependent on the interaction with the cholinergic system, as shown by the high IC50 values of A. oleracea EO and spilanthol exhibited in the anti-acetylcholinesterase (AChE) assay. Testing LC30 values, the A. oleracea-borne products showed a significant impact on larval development, fecundity, fertility and natality of C. quinquefasciatus. Testing LC30 values, the A. oleracea EO-NE provided a higher efficacy than spilanthol, reducing the adult fertility, in terms of egg hatchability (%) and the overall abundance of F1 larvae. These results can be considered as promising for the development of new mosquito larvicides. The safety use of A. oleracea EO, NE and spilanthol was demonstrated in assays on mammalian fibroblasts and microglia cells, showing low level of cytotoxicity coupled with protective effects against inflammation.

Isofuranodiene (IFD) is a sesquiterpene occurring in several plant species, which proved to have multiple anticancer activities. IFD has a lipophilic nature and, hence, a very low water solubility and a poor bioavailability; moreover, it is not stable, undergoing the "Cope rearrangement" to the less active curzerene. The use of appropriate delivery systems can thus be considered as a valid tool to enhance IFD bioavailability, solubility, stability and at the same time also to improve its intracellular uptake and pharmacological activity. Within this frame, monoolein (GMO) nanoparticles loaded with IFD were prepared and their enhanced anticancer activity, compared to pristine IFD, was assessed. In this study, for the first time, an in vitro Fourier Transform Infrared and Raman Microspectroscopy approaches were exploited to evaluate the effects of IFD, alone and loaded in GMO nanoparticles, on MDA-MB 231 breast cancer cell line. The anti-cancer effects of IFD were evidenced by both the spectroscopic techniques and discriminated from the GMO-induced changes in the culture environment; moreover, a synergistic effect of IFD and GMO administration can be envisaged by the experimental results.

There is a growing interest in the research of natural products with potent activity in the prevention and treatment of diseases. Thereby, essential oil phytochemicals have demonstrated broad bioactivities. This study highlights the chemical composition of essential oils obtained from the leaves and inflorescences of diverse species of the genus Solidago (Solidago canadensis, Solidago gigantea, Solidago virgaurea and Solidago×niederederi), also known as Goldenrod, through GC/MS analysis, and their antiproliferative activity on three human tumor cell lines (MDA-MB 231, A375 and HCT116) by the MTT assay. The most represented chemical classes in the essential oils were oxygenated sesquiterpenes, sesquiterpene hydrocarbons, oxygenated monoterpenes and monoterpene hydrocarbons, with a remarkable contribution of compounds such as germacrene D (3.89-19.51 %), α-pinene (3.59-18.82 %), bornyl acetate (3.30-12.73 %) and caryophyllene oxide (3.07-9.18 %). Chemical quali- and quantitative differences were noticed between the leaves and flowers of the same species, as well as between the studied species. The MTT assay showed that the essential oils from the leaves were more active than those from the flower ones. The essential oil having the highest impact on cell viability was that from S.×niederederi (IC50 =12.93, 6.72, and 6.82 μg/ml), followed by S. virgaurea (IC50 =13.39, 7.96, and 8.36 μg/ml) and finally S. gigantea (IC50 =18.04, 5.94, and 8.10 μg/ml) on MDA-MB 231, A375 and HCT116 cell lines, respectively. The essential oil from S. canadensis showed the lowest activity (IC50 =29.33, 12.63, and 18.03 μg/ml, respectively). Taken together, these findings highlight the Solidago species as good sources of cytotoxic compounds. Further studies are encouraged on the in vivo effects and safety of these products.

Allium subhirsutum, known as hairy garlic, is a bulbous plant widespread in the Mediterranean area and locally used as a food and spice. In the present study, the chemical profile of the ethanolic extracts from bulbs (BE) and aerial parts (APE) were analyzed by HPLC-ESI-MSn, and antioxidant properties were evaluated by DPPH, ABTS and TEAC assays. The traditional use in the diet, and the well documented biological activity of Allium species suggest a potential as a new nutraceutical. For this reason, the potential usefulness of this food can be considered in the treatment and prevention of degenerative Alzheimer disease. For this reason, acetylcholinesterase inhibitory property was investigated. Furthermore, due to the observed presence of sulfur-containing and phenolic constituents, the cytotoxicity on tumor cells line was investigated. Results revealed significant AChE inhibitory activity for BE and APE. Both extracts exhibited also moderate antioxidant properties in the in vitro assays. Finally, limited cytotoxic activity was observed towards Human colon carcinoma and adenocarcinoma cell line, with differences between the individual parts tested. HPLC-ESI-MSn analysis showed that hairy garlic is a good source of sulphur compounds, flavonoids and phenylpropanoids derivatives, thus being a valid alternative to the common garlic (A. sativum). This work opens new opportunities for the application of A. subhirsutum as a health-promoting food.

Nanoemulsions represent one of the most promising colloidal systems for the vehiculation and delivery of hydrophobic molecules, exploitable in several fields such as pharmaceutical, cosmetic, food and agricultural. In this study, we investigated the influence of the formulation parameters, in particular the type of surfactant, on the physico-chemical properties of oil in water nanoemulsions. Six different surfactants were selected based on the similar HLB value (around 15) but different chemical features, such as linear and steric hindrance molecules, PEGylated and PEG-free compounds or the presence of saturated or unsaturated fatty tails. All the surfactants were preliminary characterized in term of surface and interface tension and cytotoxicity. Nanoemulsions were then obtained through a high-pressure homogenization process and evaluated in terms of physico-chemical properties and stability (180 days). The results showed no remarkable differences in the mean diameter of nanoemulsions prepared with the six tested surfactants, suggesting that the size of the oil droplets is mainly dependent by the action of the disruptive forces generated during the homogenization process. However, the nanoemulsions stability was strongly affected by the used surfactants, varying from few weeks up to more than six months. Specifically, the polyglycerol and glucoside derived amphiphiles were the less effective while polysorbate-80 and oleth-20 were able to give optimal nanosystems in terms of both physico-chemical properties and thermodynamic stability. Interestingly, despite polysorbate 80 and oleth 20 showed comparable efficacy, their safety profiles were markedly different. Overall, it has been observed that the surfactant ability to reduce the tension at the O/W interface is closely related to the stability of the nanoemulsions, allowing the prediction of their medium or long-term stability.

There is increasing interest in the bioactivity of peptides carrying out antiproliferative, antihypertensive, antimicrobial, antioxidant, anticholesterolemic, opioid, and antidiabetic activities. The bioavailability of peptides depends on how readily they are digested by endopeptidases and their ability to pass through cell membranes, features that are determined by the peptide's chemical and physical structure. On the basis of structures present in peptides that have biological activity, particularly antiproliferative activity, the tripeptides AcGly-Phe-Asn(OH) and AcGly-Phe-Asn(NH2) have been designed and synthesized, then tested for their antiproliferative activity on human breast adenocarcinoma cells (MDA-MB 231) and human dermal fibroblasts (HuDe). The results show that the peptides significantly affect the proliferation of MDA-MB 231 and HuDe cells, with differentiated response between tumor and normal cells, and thus indicate that C-terminal amidation plays a role. Interestingly, the activity of both peptides in dermal fibroblasts follows the characteristic biphasic pattern of hormesis, a dose-response relationship.

Rosmarinus eriocalyx is an aromatic evergreen bush endemic to Algeria where it is used as a condiment to flavour soups and meat and as a traditional remedy. In the present work we have analyzed for the first time the phenolic composition of polar extracts obtained from stems, leaves and flowers of R. eriocalyx by HPLC, and determined the antioxidant and antimicrobial effects by DPPH, ABTS, FRAP, ORAC and agar disc diffusion methods, respectively. Results showed that ethanolic extracts of leaves and flowers are a rich source of phenolic compounds, mainly rosmarinic acid, carnosic acid and carnosol that are the main responsible for the noteworthy antioxidant activity observed in the assays. This study showed that R. eriocalyx might be a spice to be included in the European food additive list and used as a preservative agent besides R. officinalis.

Trachyspermum ammi (Apiaceae) is a plant with a good reputation in the traditional Persian and Ayurvedic medicine. The hydrodistilled essential oil from the fruits of T. ammi , known as ‘ajwain oil’, is used in countries such as Iraq, Iran, Afghanistan, Pakistan, and India in the preparation of curry, to flavour several foods, as preservative, and in perfumery. At therapeutic level, ajwain oil is employed in the treatment of gastrointestinal ailments, lack of appetite and bronchial problems. In the present work, the essential oil of T. ammi growing in Iran was analysed by GC–FID and GC–MS showing thymol (67.4%), p -cymene (17.9%) and γ-terpinene (11.3%) as the major constituents. Afterwards, we investigated the biological effects displayed by ajwain oil, namely the antimicrobial and antioxidant activity, the cytotoxicity on tumour cells, and the induction of lymphocyte proliferation. In addition, the inhibition on nicotinate mononucleotide adenylyltransferase (NadD), which is a promising new target for developing novel antibiotics, was evaluated. The antimicrobial effects of ajwain oil, measured by the agar disc diffusion method, were relevant, with inhibition zones higher than those of reference antibiotics, especially on Staphylococcus aureus and Candida albicans (34.7 and 54.3 mm, respectively). This effect was not due to the enzymatic inhibition on NadD. The ajwain oil exhibited a considerable dose-dependent inhibition on the ABTS radical cation, with an IC 50 value of 22.4 μg/mL. MTT assay revealed that ajwain oil is particularly cytotoxic on colon carcinoma cells, with a IC 50 value of 9.6 μg/mL. Finally, PBMC proliferation assay revealed some role for the ajwain oil within the network of interactions of the cells of the immune system.

Since time immemorial, the oleo-gum-resins of Ferula assa-foetida and F. gummosa are used in the traditional medical systems as well as in foodstuffs, perfumery and cosmetics. In the present study, we explored the insecticidal efficacy of the essential oils obtained from these oleo-gum-resins to widen their fields of industrial applications. The two essential oils were mainly composed of sulfides [sec-butyl (Z)-propenyl disulfide, sec-butyl (E)-propenyl disulfide, sec-butyl (Z)-propenyl trisulfide and sec-butyl (E)-propenyl trisulfide)] and monoterpenes (α-pinene, β-pinene and β-phellandrene), respectively, as determined by GC-MS analysis. The two essential oils were assayed for toxicity on a panel of insects, represented by species of public health relevance (Culex quinquefasciatus and Musca domestica), agricultural (Spodoptera littoralis) and stored-product pests (Prostephanus truncatus and Trogoderma granarium). The ecotoxicological effects of the essential oils were assessed on the aquatic microcrustacean Daphnia magna and the earthworm Eisenia fetida, as well as on human cells. Overall, the two essential oils were effective against important insect pests and vectors. On the other hand, they resulted cytotoxic to fibroblasts and non-target aquatic microcrustaceans. Thus, further insights are needed to determine the full spectrum of their eco-toxicological effects.

A new sulfated steroidal derivative (fruticogenin A: 1-sulfo-australigenin-3-sodium sulphate, 1) and three new steroidal saponins named fruticoside K (3-sulfo-spirostan-25(27)-ene-1β,3β-diol-1-O-[α-L-rhamnopyranosyl-(1 → 4)-β-D-fucopyranoside], 2), fruticoside L (3-sulfo-spirostan-25(27)-ene-1β,3β,6α-triol-1-O-[α-L-rhamnopyranosyl-(1 → 4)-β-D-fucopyranoside], 3) and fruticoside M (spirostan-25(27)-ene-1β,3α-diol-1-O-[α-L-rhamnopyranosyl-(1 → 2)-α-L-rhamnopyranoside], 4) were isolated from the aerial parts of Cordyline fruticosa L. var. strawberries. Their structures were established on the basis of 1D and 2D NMR data, mass spectrometry and chemical methods. Compounds 2 and 4 exhibited weak cytotoxicity against melanoma (A375), breast adenocarcinoma (MDA-MB-231), and colon carcinoma (HCT116) human tumor cell lines.

Apium nodiflorum (L.) Lag. (water celery) is an hydrophytic plant forming dense submerged populations occurring along streams and rivers of Europe. In the present work we provided new insights into...

Developing effective larvicides for mosquito control is being challenging due to the quick development of resistance in targeted vectors. Botanical products can help, due to their multiple mechanisms of action coupled with eco-friendly features. Carlina acaulis (Asteraceae) is an Alpine perennial herb used as a traditional remedy and food. Its root essential oil (EO) has antimicrobial and antitrypanosomal properties, and is currently listed among botanicals employable in food supplements. Its insecticidal activity has not been explored so far. Here, after analysing the C. acaulis EO chemical composition by GC–MS and NMR, we detected extremely high larvicidal activity of this EO and its main constituent, carlina oxide, against Culex quinquefasciatus larvae by using the standard WHO protocol. LC50 were 1.31 and 1.39 μg mL-1, respectively. 24-h exposure to both products triggered significant mortality rates for five days post-treatment. Larvicidal tests on a wider scale confirmed >95% larvicidal effectiveness of the EO and carlina oxide tested at 1.25 μg L-1. Their non-target impact was evaluated through experiments on Daphnia magna adults. Both showed significantly lower toxicity if compared to cypermethrin. To shed light on the modes of action, carlina oxide was tested for anti-acetylcholinesterase activity by the Ellman method, with lower performances over galantamine. A moderate antioxidant potential was observed using DPPH and ABTS assays, since it has a role for preserving the shelf-life of herbal-based insecticides. Finally, cytotoxicity on vertebrate cells was noted, testing carlina oxide on human dermis, HCT116 and MDA-MB231 cell lines by MTT assay. Overall, the outstanding toxicity of the tested products make them excellent candidates to develop novel mosquito larvicides for real-world applications.

Diets rich in foods containing antioxidants, such as fruits and vegetables, could help to prevent cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, cancer and slow the aging process. The aim of this work was to look at the seed sprouts of a member of the Brassica genus, Savoy cabbage (Brassica oleracea L. var. sabauda) to determine the antioxidant activity of aqueous and hydroalcoholic extracts made from powdered form of its sprouts. The in vitro antioxidant activity of extracts was tested using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging assays. A useful indicator of ROS, 2′,7′-dichlorodihydrofluorescin diacetate (H2DCF-DA), was used to determine the antioxidant and pro-oxidant activity of sprout extracts in a cell-based assay. Significant values of “in vitro” antioxidant activity were found in aqueous and hydroalcoholic extracts. Aqueous sprout extract showed a dose-dependent pro-oxidant activity, higher than hydroalcoholic extract in a cell-based assay. The pro-oxidant activity was correlated with the inhibition of cell proliferation and proved thermolabile. Practical Applications Compounds with important biological activity have been isolated and characterized from sprouts and can be used in the nutraceutical field. Sprouts contain a cocktail of antioxidant compounds that shows a strong reducing activity. The study was extended to Savoy cabbage sprout extracts using cell-based assay. Antioxidant and pro-oxidant activities were put in evidence. The present results draw attention to the real antioxidant capacity of a plant extract. An adequate assessment of the antioxidant capacity should take in account the pro-oxidant activity of an extract.

Two new cocrystalline compounds, (Hen)(H2L2)·2/3H2O (2) and (Him)(H3L3)·2H2O (8), were prepared by the reaction of 5-(2-(4-chlorophenyl)hydrazono)pyrimidine-2,4,6(1H,3H,5H)-trione (H3L2) and the sodium salt of 2-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazinyl)benzenesulfonic acid (H4L3), [Na(H3L3)(μ-H2O)(H2O)2]2 (1) with protonated ethylenediamine (Hen) and imidazole (Him), respectively. By using 5-(2-(2-hydroxyphenyl)hydrazono)pyrimidine-2,4,6(1H,3H,5H)-trione (H4L1) and 1, several known CuII, CoII, CoII/III and new AgI complexes, [Cu(H2L1)(H2O)(im)]·3H2O (3), [Co(H2O)6][Co(H2L1)2]2·8H2O (4), [Co(H2L3)(im)3] (5), [Cu(H2L3)(im)2]·H2O (6), [Ag(H2O)(μ-H3L3)]n (7) and [Co(H2O)6][H3L3]2·8H2O (9), were also prepared in order to study their DNA and BSA binding, anticancer and antimicrobial properties. The complexes are able to interact with DNA and BSA with high binding constant values. In particular, complex 4 strongly intercalates DNA and binds BSA. The antimicrobial activity of all compounds, determined against a panel of reference bacterial and fungal strains, indicates that only 2 and 7 possess antimicrobial activity. The same compounds 2 and 7 show a pronounced antiproliferative activity against the human tumor cell lines A375, MDA-MB 231 and HCT116.

Isofuranodiene is an oxygenated sesquiterpene containing a furan ring isolated from the essential oil of Smyrnium olusatrum L. (Apiaceae) owning notable anticancer activity. Despite its biological potential, the high lipophilicity along with a relatively low stability due to Cope rearrangement giving rise to a less active compound, make the perspective of its therapeutical use unlikely. On this basis, in the present work we evaluated bulk and dispersed non lamellar liquid crystalline phases as effective delivery vectors for isofuranodiene, and capable of preserving its structure and enhancing the biological activity. Small-angle X-ray scattering, dynamic light scattering, and UV resonance Raman spectroscopy were used to characterize the nanosystems in an integrated experimental approach. Encapsulation of isofuranodiene in the lipid matrix resulted in a transition from a cubic Im3m to a reversed hexagonal phase because of the highly lipophilic character of the drug, as obtained in SAXS measurements, and in significant shifts in the components of the Raman spectrum of isofuranodiene. The anticancer activity of isofuranodiene-loaded lipidic nanoparticles was assessed on MDA-MB 231 cell line by MTT assay and was found to be higher than that of pristine isofuranodiene.

Tansy daisy (Tanacetum macrophyllum (Waldst. et Kit.) Schultz Bip., Asteraceae) is a perennial herb worldwide cultivated for ornamental and industrial purposes. Sometimes, this species is misidentified by herb collectors and botanists with its family mate Achillea grandifolia (white yarrow). In the present work, we have analysed the essential oil and ethanolic extract obtained from the aerial parts of tansy daisy cultivated in Italy and evaluated the biological activity in terms of cytotoxic, antioxidant and anticholinesterase activities. The essential oil was analysed by gas chromatographic and mass spectrometry (GC–MS) and showed oxygenated monoterpenes, namely camphor, linalool and 1,8-cineole, and sesquiterpenes, namely germacrene D and 10-epi-γ-eudesmol, as the major components. The ethanolic extract of aerial parts was subjected to chromatographic separation and this permitted the identification of 12 polar compounds belonging to five different classes of natural products, namely flavonoids (apigenin, cirsimaritin, apigenin-7-O-glucoside, apigenin-7-O-glucuronide, kaempferol-7-O-glucoside and kaempferol-7-O-glucuronide), dicaffeoylquinic derivatives (3,5-dicaffeoylquinic and 4,5-dicaffeoylquinic acids), caffeoylquinic acids (chlorogenic acid), free organic acids (shikimic and quinic acids) and glycosidic organic acids (4-O-β- d -glucopyranosyl-vanillic acid); among them apigenin and kaempferol derivatives were the most abundant. Finally, the essential oil from the leaves, containing high levels of germacrene D and 10-epi-γ-eudesmol, was highly effective against the proliferation of A375 (melanoma) and HCT116 (colon carcinoma) human tumor cells, showing IC50 values of 9.2 and 8.5 μg/mL, respectively. On the other hand, the ethanolic extract scavenged the DPPH and ABTS + radicals, showing IC50 of 32.7 and 37.2 μg/mL, respectively. The inhibitory properties of tansy daisy essential oils and ethanol extract on the acetylcholinesterase enzyme were also evaluated. These findings provided new insights into the phytochemistry of the species and its possible applications on an industrial level.

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 -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 m, which make it a promising anticancer drug candidate.

The relationship between diet and health has drawn ever-growing interest. Bioactive peptides are involved in various biological activities, including control of cell proliferation, antimicrobial, antihypertensive, antioxidant, anticholesterolemic, and opioid activity. However, the peptide potential activity is quenched by some factors such as peptide digestion by proteases, cell membrane permeability, and clearance by kidney function. These obstacles to peptide bioavailability are increased for the nutraceutical use of peptides. The aim of this paper is to review the biochemical peculiarities that can improve the nutraceutical use of peptides. The involvement of amino acid sequence, N- and C-terminal groups, and internal chemical modifications of peptide are reported and discussed. In particular, the block of N-terminal group (N-acetylation, or presence of pyroGlu) or/and of C-terminal group (C-amidation), as well as the Ser/Thr/Tyr phosphorylation, prevent the peptide hydrolysis by digestive proteases and give them a better chance to enhance penetration of biological barriers.

Stachys annua subsp. annua, well-known in central Italy as 'stregona annuale', is an annual, small, slightly-scented herb, commonly found in fields and uncultivated areas in almost all regions of Italy. In folk medicine, its aerial parts were used as anti-catarrhal, febrifuge, tonic, and vulnerary. In the present work, the chemical composition of the flowering aerial parts was studied. The hydrodistilled volatile oil, analysed by GC/MS, showed sesquiterpenoids as the major fraction (42.5%); phytol (9.8%), germacrene D (9.2%), and spathulenol (8.5%) were the most abundant constituents. The volatile oil was assayed for antioxidant and cytotoxic activity by DPPH, ABTS, FRAP, and MTT methods. The cytotoxicity results against HCT116, A375, and MDA-MB 231 human tumor cell lines were significant, with IC50 values of 23.5, 37.2, and 41.5 μg/ml, respectively, whereas the antioxidant power was negligible. The EtOH extract was composed mainly of three glycosidic flavonoids, namely 7-{[2-O-(6-O-acetyl-β-D-allopyranosyl)-β-D-glucopyranosyl]oxy}-5,8-dihydroxy-2-(4-methoxyphenyl)-4H-1-benzopyran-4-one (1), 7-{[6-O-acetyl-2-O-(6-O-acetyl-β-D-allopyranosyl)-β-D-glucopyranosyl]oxy}-2-(3,4-dihydroxyphenyl)-5,8-dihydroxy-4H-1-benzopyran-4-one (2), and 7-{[6-O-acetyl-2-O-(β-D-allopyranosyl)-β-D-glucopyranosyl]oxy}-2-(3-hydroxy-4-methoxyphenyl)-5,8-dihydroxy-4H-1-benzopyran-4-one (3). On the contrary, iridoids, considered chemotaxonomic markers of the genus Stachys, were absent in this species. Finally, the morphological and histochemical survey showed that glandular trichomes were composed of two main types, i.e. peltate type A and capitate types B and C giving positive response for both lipids and polyphenols.

Eryngium campestre and E. amethystinum are thorny herbs belonging to the Apiaceae family and spontaneously growing in stony pastures and dry meadows, preferentially on calcareous substrates. In the Mediterranean countries, these plants have been used as a food or traditional remedies to treat various ailments. In the present work, we have analysed the chemical composition of the essential oils distilled from the aerial parts by GC-FID and GC-MS, and evaluated their cytotoxic effects on a panel of human cancer cells, namely A375 (human malignant melanoma), MDA-MB 231 cells (human breast adenocarcinoma) and HCT116 cells (human colon carcinoma), by the MTT assay. Furthermore, the Eryngium essential oils were evaluated for antioxidant and acetylcholinesterase (AChE) activities. The two essential oils were rich in sesquiterpene hydrocarbons, with germacrene D as the major compound, accompanied by allo-aromadendrene, β-elemene, spathulenol and ledol. They resulted highly cytotoxic on the tumor cells, with IC50 values (1.65-5.32 and 1.57-2.99 μg/ml for E. amethystinum and E. campestre, respectively) comparable or close to those of the anticancer drug cisplatin. The E. amethystinum essential oil exhibited a moderate antioxidant activity whereas that of E. campestre a weak AChE inhibition. This article is protected by copyright. All rights reserved.

Context:Thymus alternans Klokov (Lamiaceae) is a neglected species of the genus Thymus (Sect. Serpyllum) endemic to Carpathian area, where it is used as a flavouring agent and for medicinal purposes. Objective: The aim of the work was to identify antiproliferative constituents from the flowering aerial parts of this plant. Materials and methods:Thymus alternans extracts were analyzed by HPLC-MSn and subjected to extensive chromatographic separations. The isolated compounds (phenolics and triterpenes) were structurally elucidated by MS and 1D and 2D NMR experiments. Essential oil (EO) composition was determined by GC-FID and GC-MS. Six purified triterpenes and EO were assayed for in vitro antiproliferative activity against a panel of human cancer cells, namely, breast (MDA-MB 231), colon (HCT-15 and HCT116), lung (U1810), pancreatic (BxPC3), melanoma (A375) and cervical carcinoma (A431) cells. Results: The structures of the isolated compounds were achieved on the basis of H-NMR and MS experiments. Luteolin-4′-O-β-d-glucopyranoside (P1), chrysoeriol-7-O-β-d-glucopyranoside (P2), chrysoeriol-5-O-β-d-glucopyranoside (P3), apigenin-7-O-β-d-glucopyranoside (P4), rosmarinic acid (P5), rosmarinic acid-3′-O-β-d-glucopyranoside (P6), caffeic acid-3-O-β-d-glucopyranoside (P7), 3α-hydroxy-urs-12,15-diene (T1), α-amyrin (T2), β-amyrin (T3), isoursenol (T4), epitaraxerol (T5), and oleanolic acid (T6). GC-MS analysis revealed that the EO of T. alternans was devoid of phenols and belonged to the nerolidol-chemotype, that is typical of the Sect. Serpyllum. The six purified triterpenes (T1-T6) were active with IC50 ranging from 0.5 to 5 μM being comparable or better than those of reference compounds betulinic acid and cisplatin. The EO exhibited significant effects on A375, MDA-MB 231 and HCT116 cell lines with IC50 in the range of 5–8 μg/mL. Conclusion: The reported results suggest that T. alternans can be considered as a good source of phytoconstituents with possible importance in the pharmaceutical field.

Smyrnium olusatrum L. is a horticultural crop cultivated during the Roman age for culinary and curative uses. The essential oil extracted from this plant (AEO) is rich in bioactive constituents such as isofuranodiene and germacrone. Several previous studies revealed that AEO and its isolated components possess interesting therapeutic features, such as antiproliferative, neuritogenic, hepatoprotective and antioxidant properties. Nevertheless, AEO has stability problems because of the high concentration of its main components. This issue makes AEO very difficult to handle and use. Thus, AEO was formulated as microemulsions known for their thermodynamic stability and easiness of preparation. AEO was hydrodistilled from inflorescences of S. olusatrum and its composition determined by different chromatographic methods. The microemulsions were developed using a central composite design and their activity tested using the MTT assay. The present study demonstrated the possibility to formulate stable AEO microemulsions where the crystallization of isofuranodiene is avoided, and the AEO biological activity is maintained. Copyright © 2016 John Wiley & Sons, Ltd.

Magnolia grandiflora (Magnoliaceae) is an evergreen tree with fragrant and showy flowers native to southeastern USA but widely cultivated all over the world and used in cosmetics industry in treatment of skin diseases. Here, we report on the chemical analysis of the essential oil obtained from flowers of plants cultivated in Iran, together with the evaluation of its antioxidant and cytotoxic activities. The essential oil composition was dominated by bioactive sesquiterpenes, namely β-elemene, bicyclogermacrene, germacrene D and (E)-caryophyllene. The oil exhibited moderate radical scavenging activity towards the radical, and mild non-selective inhibitory effects against A375, MDA-MB 231 and T98 G tumour cell lines. The latter were influenced by the presence of the anticancer β-elemene. These results provided new insights for potential application of M. grandiflora volatile oil in the pharmaceutical and cosmetics industry where only the non-volatile magnolol and honokiol have hitherto been fully exploited.

Fruits of Xylopia parviflora, well known as striped African pepper, are sold in the Cameroonian markets as a flavouring ingredient to make traditional soups. The essential oil hydrodistilled from fruits was analysed for in vitro biological activities, namely cytotoxic, anti-inflammatory, antimicrobial and antioxidant, by MTT, nitric oxide inhibitory assay, agar disc diffusion method, and DPPH and ABTS assays. The essential oil composition, analysed by GC and GC-MS, was dominated by monoterpene hydrocarbons (50.0%) responsible for the pepper odour, such as β-pinene (34.0%) and α-pinene (10.3%). The oil induced a strong inhibitory effect on tumour cells MDA-MB 231 and HCT116, with inhibition values close to those of cisplatin. A dose-dependent decrease in NO production was noted in RAW 264.7 macrophages treated with the oil, revealing a promising anti-inflammatory potential. The essential oil showed a measurable antimicrobial activity against all the species tested, while the radical scavenging activity was low.

The antineoplastic potential of a new stable mixed phosphine gold(I) complex containing tris(tert-butyl)phosphine (tBu 3 P) and bis(diphenylphosphino)ethene (dppet), namely [Au(tBu 3 P)(dppet)Cl], has been investigated in the human colon cancer HCT-116 cell line. The 31 P NMR solution study, confirms the structural features observed in the solid state and, in addition, indicates partial formation of dinuclear cationic [Au(tBu 3 P) 2 ] + and [Au(dppet) 2 ] + species. The ionic character and strong Au–P bonds of this gold(I) species are similar to those of the most active antitumor gold compounds so far studied. The title compound was found to exhibit strong cytotoxicity, showing 85 fold greater toxicity than cisplatin (IC 50 = 0.45 μM vs IC 50 = 39.16 for cisplatin at 24 h) on the HCT-116 line. The cytotoxic effects were, at least partly, mediated by the induction of apoptotic cell death as evidenced by the sub-G 1 cell accumulation, oligonucleosomal DNA fragmentation, caspase-3 activation and the release of cytochrome c from the mitochondria. The gold(I) compound showed little interaction with DNA measured through fluorescence quenching studies with calf thymus DNA. The inhibitory effect of the gold(I) compound on intracellular redox proteins has been also observed in pretreated HCT-116 cells. The compound was particularly effective in inhibiting thioredoxin reductase, that is likely responsible for the increased ROS production, and subsequent apoptosis induction via the mitochondrial pathway.

This study was undertaken to assess the antioxidant and antiproliferative potential of the essential oil of Hypericum hircinum L. subsp. majus (Aiton) N. Robson. Analysis of the oil composition revealed that sesquiterpene hydrocarbons (69.3%) dominate, cis-β-guaiene, δ-selinene and (E)-caryophyllene being the most representative. Significant values of antioxidant activity were found using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging assays. The essential oil revealed antiproliferative activity as evaluated on human glioblastoma (T98G), human prostatic adenocarcinoma (PC3), human squamous carcinoma (A431) and mouse melanoma (B16-F1) tumour cell lines by MTT assay.

Vepris macrophylla is an evergreen tree occurring in sub-humid forest of Madagascar and traditionally used in the Island to treat several complaints as well as to prepare aromatic teas and alcoholic drinks. In the present work, the essential oil distilled from the leaves was analyzed for the first time by gas chromatography (GC-FID) and gas chromatography/mass spectrometry (GC/MS). The major compounds were citral (56.3%), i.e., mixture of neral (23.1%) and geranial (33.2%), citronellol (14.5%), and myrcene (8.3%). The essential oil exhibited antimicrobial activity against S. aureus, P. aeruginosa, and C. albicans as determined by vapor-diffusion assay, supporting the traditional use of the plant for preparing steam bath for the treatment of infectious diseases. The essential oil was evaluated for cytotoxic activity on human tumor cell lines by MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, showing inhibitory effects comparable to those of cisplatin, notably on MDA-MB 231 (human breast adenocarcinoma) and HCT116 (human colon carcinoma) cell lines. Finally, the essential oil was also subjected to screening for its antioxidant activity and the free radical scavenging capacity.

Ajuga chamaepitys (L.) Schreb, well-known as Camaepitium or Ground Pine, is an annual herb typical of the Mediterranean area accounting several uses in the traditional medicine. In this work we have, analyzed the plant iridoid fraction together with the essential oil composition and study of the plant indumentum. Finally, we assayed the polar extracts and essential oil obtained from the aerial parts for antioxidant activity and cytotoxicity on tumor cells. The analysis of the monoterpene glycosides allowed us to isolate from roots and aerial parts and to structurally elucidate by NMR and MS the following compounds: ajugoside (1), reptoside (2), 8-O-acetylharpagide (3), harpagide (4), 5-O-β-d-glucopyranosyl-harpagide (5), asperulosidic acid (6), deacetyl asperulosidic acid (7) and 5-O-β-d-glucopyranosyl-8-O-acetylharpagide (8), among which 5 and 8 were two new natural products. Chemotaxomic relevance of these constituents was discussed. The chemical analysis of A. chamaepitys essential oil by GC-FID and GC-MS showed ethyl linoleate (13.7%), germacrene D (13.4%), kaurene (8.4%), β-pinene (6.8%), and (E)-phytol (5.3%) as the major volatile components. The micromorphological and histochemical study showed that iridoids and essential oil are mainly produced in the type III capitates and peltate trichomes of leaves and flowers. Biological evaluations of A. chamaepitys polar extracts and essential oil showed that the former were more potent as radical scavengers than the latter. MTT assay revealed that essential oil and ethanolic extracts were moderately cytotoxic on tumor cells with IC50 of 36.88 and 59.24μg/mL on MDA-MB 231 cell line, respectively, and IC50 of 60.48 and 64.12μg/mL on HCT116, respectively.

The industrial extraction and further applications of isofuranodiene are limited because at room temperature it spontaneously converts to curzerene, a structurally less active isomer. This work definitively identified the structure of isofuranodiene in the solid state, showing the two methyl groups in syn position. In addition, two bioactive metal cations, namely, silver(I) and copper(II) ions, were used in the attempt to obtain the chemical stability of isofuranodiene: in the case of silver(I), a labile adduct was formed, while in the case of copper(II), a more stable 1:1 adduct was achieved. In the former, the presence of silver did not significantly affect the biological activities of isofuranodiene, while in the latter, the copper(II) coordination suppressed them. The biological activities of the isofuranodiene adducts were then evaluated as antiproliferative agents against human tumor cell lines (HCT116, MDA-MB 231, and T98G). In addition, for the first time, isofuranodiene was tested as an inhibitor of DHFR (DiHydroFolateReductase) from Escherichia coli. Anticancer activity was observed in the isofuranodiene with the AgCF3SO3 adduct, in the tested cell lines, with IC50 values ranging from 4.89 μM to 13.06 μM, while inhibition assays highlighted a Ki of 6.22 μM for isofuranodiene and of 0.17 μM for the related silver adduct. Docking studies indicated a binding mode score of − 6.83 Kcal/mol for isofuranodiene, and an energy value of − 11.82 Kcal/mol for methotrexate (a classic DHFR inhibitor).

Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in the Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities. Moreover, we investigated the inhibitory effects of E. floribundus essential oil on nicotinate mononucleotide adenylyltransferase (NadD), a promising new target for developing novel antibiotics, and Trypanosoma brucei, the protozoan parasite responsible for Human African trypanosomiasis. The essential oil composition was dominated by spathulenol (12.2%), caryophyllene oxide (12.4%) and limonene (8.8%). The E. floribundus oil showed a good activity against Staphylococcus aureus (IZD of 14 mm, MIC of 512 µg/mL). Interestingly, it inhibited the NadD enzyme from S. aureus (IC50 of 98 µg/mL), with no effects on mammalian orthologue enzymes. In addition, T. brucei proliferation was inhibited with IC50 values of 33.5 µg/mL with the essential oil and 5.6 µg/mL with the active component limonene. The essential oil exhibited strong cytotoxicity on HCT 116 colon carcinoma cells with an IC50 value of 14.89 µg/mL, and remarkable ferric reducing antioxidant power (TEAC= 411.9 μmol TE/g).

Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study, we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities. Moreover, we investigated the inhibitory effects of E. floribundus essential oil on nicotinate mononucleotide adenylyltransferase (NadD), a promising new target for developing novel antibiotics, and Trypanosoma brucei, the protozoan parasite responsible for Human African trypanosomiasis. The essential oil composition was dominated by spathulenol (12.2%), caryophyllene oxide (12.4%) and limonene (8.8%). The E. floribundus oil showed a good activity against Staphylococcus aureus (inhibition zone diameter, IZD of 14 mm, minimum inhibitory concentration, MIC of 512 mu g/mL). Interestingly, it inhibited the NadD enzyme from S. aureus (IC50 of 98 mu g/mL), with no effects on mammalian orthologue enzymes. In addition, T. brucei proliferation was inhibited with IC50 values of 33.5 mu g/mL with the essential oil and 5.6 mu g/mL with the active component limonene. The essential oil exhibited strong cytotoxicity on HCT 116 colon carcinoma cells with an IC50 value of 14.89 mu g/mL, and remarkable ferric reducing antioxidant power (tocopherol-equivalent antioxidant capacity, TEAC = 411.9 mu mol.TE/g).