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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.

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.

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.

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.

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.

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.

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.

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.

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).

Sideritis montana subsp. montana is a small annual herb occurring in countries bordering the Mediterranean and Balkan regions. The secondary metabolism of this plant has not been fully explored so far. The aim of the present study was to understand the complex mixture of secondary metabolites and the type of secretory structures. The polar constituents were isolated by column chromatography from the ethanolic extract, and their structure was elucidated by NMR and MS. The essential oil was isolated by hydrodistillation and analysed by GC/MS. The plant indumentum was studied by light and scanning electron microscopy. To complete the work, the essential oil antioxidant activity and cytotoxicity on tumor cells were evaluated by DPPH, ABTS, FRAP, and MTT methods. Four different classes of secondary metabolites were isolated, namely flavonoids, caffeoylquinic derivatives, glycosidic hydroquinones and iridoids. The essential oil was mainly characterized by sesquiterpenene hydrocarbons. Peltate and long-capitate hairs were the main sites where terpenes and polar constituents are produced. The secondary metabolites found in S. montana subsp. montana are of chemotaxonomic interest, some of them being typical of the genus Sideritis. The trichomes types observed partially differ from those described in other members of the genus Sideritis. The essential oil showed noteworthy inhibition on tumor cells.

Schizogyne sericea (Asteraceae) is a halophytic shrub endemic to the Canary Islands and traditionally employed as analgesic, astringent, anti-inflammatory, and vulnerary. A comprehensive phytochemical investigation was conducted on the flowering aerial parts by analyzing both essential oil constituents and polar compounds. The essential oil was dominated by p-cymene, with the noteworthy occurrence of β-pinene and thymol esters. From the EtOH extract, eight compounds were isolated and structurally elucidated. Essential oil, polar fractions, and isolates (2), (4), and (5) were separately in vitro assayed for antiproliferative activity on human tumor cell lines (A375, MDA-MB 231, and HCT116) by MTT assay, for antioxidant potential by DPPH, ABTS, and FRAP assays, and for antimicrobial activity by the agar disk diffusion method. Results revealed that essential oil and compounds 1 and 2 exert a strong inhibition on tumor cells, and in some cases, higher than that of cisplatin. Fractions containing thymol derivatives (1 and 2) and caffeoylquinic acid derivatives 4 and 5 displayed antioxidant activity comparable to that of Trolox, making S. sericea extract an interesting natural product with potential applications as preservative or in the treatment of diseases in which oxidative stress plays an important role.

Tithonia diversifolia , well-known as Mexican sunflower, is an invasive shrub growing in tropical areas of South America, Asia and Africa where it is used as a traditional medicine, ornamental plant and green biomass to improve soil fertility. Given the traditional uses in the treatment of skin infections, we have first analysed the chemical composition and the antimicrobial effects of the essential oil hydrodistilled from inflorescences of T . diversifolia . For the purpose the inhibition zones against a panel of pathogens were measured by the agar diffusion method. In addition, we evaluated the inhibitory effects on several NaMN/NMN adenylyltransferases, which are essential enzymes for NAD biosynthesis in most bacterial pathogens, and also tested the inhibition on the mammalian orthologue enzymes as a promising way to identify novel natural antibiotics. To complete the screening of biological effects, the antioxidant capacity and antiproliferative effects on human tumor cells were evaluated using the DPPH, ABTS, FRAP, and MTT methods. Results showed that T . diversifolia essential oil was mostly active against Staphylococcus aureus with a halo of 14 mm. The essential oil selectively inhibited in vitro the pure NAD biosynthetic enzyme NadD from S . aureus (IC 50 of ∼60 μg/mL), with basically none or only minor effects on mammalian orthologue enzymes. Finally, the essential oil displayed significant cytotoxic effects on A375, MDA-MB 231, HCT 116 and T98 G tumor cells with IC 50 values of 3.02, 3.79, 3.46 and 12.82 μg/mL, respectively, and noticeable radical scavenging activity on DPPH and ABTS radicals, with IC 50 values of 108.8 and 41.7 μg/mL, respectively.

Cedronella canariensis is a lemon-scented species of the family Lamiaceae endemic to the Canary Islands where it is used in the traditional medicine to prepare infusions or inhalations for anti-catarrhal, tonic, diuretic, hypoglycaemiant, hypotensive, anti-inflammatory and decongestant of the respiratory tract. In this work we investigated for the first time the antioxidant activity of the essential oil and its inhibitory effects on tumour cells (A375, MDA-MB-231, HCT 116) proliferation by DPPH, ABTS, FRAP and MTT assays, respectively. The oil, analysed by GC-ionisation flame detector and GC-MS, was characterised by pinocarvone (58.0%) and β-pinene (10.8%) as the major constituents, being typical of the chemotype 'canariensis'. Noteworthy was the cytotoxic activity of the oil against the tumour cells examined, with IC50 values of 4.3, 7.3 and 11.4 μg/mL on A375, MDA-MB-231 and HCT 116 tumour cells, respectively, as well as the scavenging activity against the ABTS radical (IC50 of 10.5 μg/mL).

Chemotypes, chemically distinct entities within a plant species based on genetic variation, are exceptionally frequent for secondary compounds such as essential oils and can influence the quality/activity of plant materials. This is the case with hyssop ( Hyssopus officinalis ) which is present in Italy with two main subspecies, officinalis and aristatus . While many phytochemical investigations have examined the former, there is a dearth of studies on the latter. In this work, we studied the morphology and histochemistry of H. officinalis subsp. aristatus growing in Abruzzo (central Italy), and conducted comprehensive phytochemical analysis of it. Furthermore, the cytotoxic, antioxidant, antimicrobial and immunostimulant effects of the essential oil were investigated. The essential oil composition, analysed by GC-FID and GC–MS, highlighted a peculiar chemotype, with linalool and methyl eugenol its main constituents. We also investigated the main chemical variations between dry and fresh batches collected in two different years. Furthermore, from the ethanolic extract, triterpenic acids, quinic acid derivatives, polyphenolic acids and, interestingly, an iridoid precursor, were isolated and structurally characterized by NMR. Study of the plant indumentum showed that the glandular trichomes vary in structure, distribution, secretion mode and in the chemical composition of the secretory products. Finally, the biological assays conducted on the essential oil highlighted moderate antioxidant and antimicrobial activity, noticeable cytotoxicity on human tumor cells and potential immunostimulant effects that are worthy of further investigations.

Helichrysum microphyllum Cambess. subsp. tyrrhenicum Bacch., Brullo e Giusso (Asteraceae), previously known as Helichrysum italicum ssp. microphyllum (Willd.) Nyman, is one of the many endemic species growing in Sardinia, Corsica and Balearic Islands. In the present work the composition of the essential oil obtained from a population of H. microphyllum ssp. thyrrenicum growing in a littoral location of La Maddalena Archipelago was investigated by GC-FID and CG-MS. The major compounds of the oil were the monoterpene ester neryl acetate (18.2%), the oxygenated sesquiterpene 5-eudesmen-11-ol (rosifoliol, 11.3%), the sequiterpene hydrocarbons δ-cadinene (8.4%) and γ-cadinene (6.7%), showing a peculiar composition in comparison with other Sardinian populations. The oil was tested for cytotoxicity on three human tumor cell lines (MDA-MB 231, HCT116 and A375) by MTT assay showing a strong inhibitory activity on human malignant melanoma cells A375 (IC50 of 16 µg/ml). In addition the oil was assessed for antioxidant activity by DPPH and ABTS assay.

The purpose of this study was to investigate the composition of the essential oil obtained from a population of Artemisia caerulescens subsp. densiflora growing in Razzoli, an island in the La Maddalena Archipelago (Sardinia, Italy). A. caerulescens sups. densiflora Viv. (Asteraceae), a wild herb, seldom studied in the Mediterranean, represents one of the many rare endemic species growing in North Sardinia. The essential oil composition was analysed by means of GC/MS analysis, which showed davana ethers as the major volatile components, accounting together for 17.5%, followed by (E)-nerolidol (4.5%), β-oplopenone (3.3%), cis-sabinene hydrate (5.2%) and terpinen-4-ol (4.7%). The oil was tested for antioxidant activity by means of DPPH test, inhibition of lipid oxidation test and hypochlorous acid test, which showed a quite interesting scavenger capacity. For the first time, we reported the cytotoxic activity of the essential oil of A. caerulescens subsp. densiflora, against three human tumour cell lines (A375, MDA-MB231 and HCT116), with IC50 values in the range 5.20–7.61 μg/mL, which deserved further studies to support its use as chemopreventive agent. Finally, the antimicrobial activity of the essential oil, displayed on a panel of human pathogens, was very low. Artemisia caerulescens subsp. densiflora (Viv.) Gamisans ex Kerguélen & Lambinon (Asteraceae)

The essential oil obtained from the fruits of hogweed (Heracleum sphondylium subsp. ternatum) growing in central Apennines (Italy) was analysed for chemical composition by gas chromatographic-flame ionisation detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The oil was composed mainly of aliphatic esters (86.9-89.5%), among them octyl acetate (54.9-60.2%) and octyl butyrate (10.1-13.4%) were the most abundant. The oil and its two major esters, octyl acetate and octyl butyrate, were tested for in vitro biological activity, namely antibacterial, antioxidant and cytotoxic, by microdilution, DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assays. Worthy of mention was only the cytotoxic activity of the oil against two tumour cell lines, i.e. A375 (human malignant melanoma) and HCT116 (human colon carcinoma) cells, with IC50 values of 48.69 and 95.83 μg/mL, respectively; the major compound responsible for this effect was octyl butyrate which displayed IC50 values of 20.19 μg/mL (100.8 μM) and 55.35 μg/mL (276.3 μM) on the same cells, respectively.

Smyrnium olusatrum (Apiaceae), well known as wild celery, is a biennal celery-scented plant used for many centuries as a vegetable, then abandoned after the introduction of celery. In the present work, the essential oil obtained from inflorescences and the amounts of its main constituents isofuranodiene, curzerene and germacrone were analyzed by GC as well as by HPLC because of their degradation (Cope rearrangement) occurring at high temperatures. The oil and the main constituents were assayed for cytotoxic activity on the human colon cancer cell line (HCT116) by MTT assay. Flower oil and isofuranodiene showed noteworthy activity on tumor cells with IC50 of 10.71 and 15.06 μg/ml, respectively. Analysis of the cytotoxic activity showed that wild celery oil and isofuranodiene are able to induce apoptosis in colon cancer cells in a time and concentration-dependent manner suggesting a potential role as models for the development of chemopreventive agents.

Stachys tymphaea (Lamiaceae) is a perennial herb growing in forest openings and dry meadows of central and southern Italy. It was investigated for the first time here, determining the content of secondary metabolites, the micromorphology of glandular trichomes, the histochemical localization of secretion, and the biological activity of the volatile oil, namely, the cytotoxic, antioxidant, and antimicrobial properties. The plant showed a peculiar molecular pattern, being rich of biophenolic compounds as flavonoids, phenylethanoid glycosides, and caffeoylquinic acid derivatives, but poor of iridoids, which are known as marker compounds of the genus Stachys. The essential oil was characterized by GC-FID and GC/MS analyses, revealing a high percentage of sesquiterpene hydrocarbons (54.6%), with germacrene D (30.0%) and (E)-β-farnesene (12.4%) as the most abundant compounds, while other main components were representatives of the diterpenes (19.2%), represented mainly by (E)-phytol (11.9%). This composition supported the taxonomic relationships in the genus Stachys, which comprises oil-poor species producing essential oils rich in hydrocarbons, with germacrene D as one of the predominant components. The micromorphological study revealed three types of glandular hairs, i.e., Type A peltate trichomes, being the primary sites of essential oil biosynthesis, Type B short-stalked trichomes, typical mucopolysaccharide producers, and Type C long capitate trichomes, secreting a complex mixture of both lipophilic and hydrophilic substances, with a major phenolic fraction. Moreover, the MTT assay revealed the potential of the volatile oil to inhibit A375, HCT116, and MDA-MB 231 tumor cells lines (IC50 values of 23.9-34.4 μg/ml).

a ) b The essential oil obtained from hydrodistillation of flowering aerial parts of Athanasia brownii (Asteraceae) was studied for its chemical composition by GC/FID and GC/MS, and for biological activity, namely, antioxidant, antimicrobial, and chemopreventive potential, by DPPH ( ¼ 2,2-diphenyl-1- picrylhydrazyl), ABTS ( ¼ 2,2'-azinobis(3-ethylbenzothioline-6-sulfonic acid), and FRAP ( ¼ ferric reducing antioxidant power), disk diffusion test, and MTT ( ¼ 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe- nyltetrazolium bromide) assay, respectively. The oil was characterized by a high content of oxygenated sesquiterpenes (71.2%), with selin-11-en-4a-ol (24.6%), caryophyllene oxide (8.7%), humulene epoxide II (5.1%), and (E)-nerolidol (4.9%) as the predominant compounds. The oil showed a moderate activity against streptococci as well as radical-scavenging potential, while the inhibitory effects against human cancer cells examined such as A375 (malignant melanoma) and HCT 116 (colon carcinoma) were significant, with IC50 values of 19.85 and 29.53 mg/ml, respectively.

The essential oils of Artemisia arborescens growing in Sardinia (Italy), collected during three plant growth stages, i.e., from the vegetative stage to post-blooming time, were characterized. Moreover, the in vitro antiproliferative and antioxidant activities of the oil isolated from aerial parts collected in February were evaluated. The essential oils belonged to the β-thujone/chamazulene chemotype, notably with the highest amount of chamazulene (ca. 52%) ever detected up to now in the genus Artemisia and, in general, in essential oils. Quantitative variations in the oil composition were observed as the plant passes from the vegetative to the blooming stage. The oil was tested for its potential tumor cell growth-inhibitory effect on T98G, MDA-MB 435S, A375, and HCT116 human cell lines, using the MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The highest activity was observed on A375 and HCT116 cell lines, with IC50 values of 14 μg/ml. Moreover, the in vitro antioxidant and free radical-scavenging assays revealed the oil to be an effective scavenger of the ABTS radical cation, with an activity comparable to that of Trolox(®) . These results support the use of A. arborescens oil for the treatment of inflamed skin conditions. Finally, the composition of the polar fraction of the A. arborescens aerial parts was also examined, and the main component detected was 5-O-caffeoylquinic acid, which was identified for the first time in this plant.

Stachys alopecuros subsp. divulsa (Lamiaceae), a perennial herb endemic to central Italy growing on mountain pastures, was investigated for the first time for the content of secondary metabolites, for the micromorphology and histochemistry of glandular trichomes, and for the biological activity of the volatile oil, namely cytotoxic, antioxidant and antimicrobial. The plant showed the molecular pattern of iridoids, among which a new iridoid diglycoside (4′- O -β- d -galactopyranosyl-teuhircoside) was detected, together with a sterol glucoside and a phenylethanoid glycoside. The essential oil from the flowering aerial parts was characterized by a high proportion of sesquiterpene hydrocarbons (65.1%), with ( E )-caryophyllene (33.2%) as the most abundant, while other main components were germacrene D (7.6%), α-humulene (6.4%) and the oxygenated cis -sesquisabinene hydrate (10.2%). Taken together, polar and apolar chemical profiles support the classification of the species within the section Betonica of the genus Stachys . Micromorphological study revealed three types of glandular hairs secreting different classes of compounds, with type A peltate hairs producing the bulk of the essential oil. MTT assay revealed the potential of the volatile oil in inhibiting A375, HCT116 and MDA-MB 231 tumor cells (IC 50 values below 20 μg/ml).

The essential oil of the 'resurrection plant' Myrothamnus moschatus (Baillon) Niedenzu endemic to Madagascar, where it is used in traditional medicine, was investigated for the first time for some biological activities. GC-FID and GC-MS analyses revealed trans-pinocarveol (35.6%), pinocarvone (20.0%), β-selinene (8.5%) and perillyl acetate (6.0%) as the major essential oil constituents. The oil strongly inhibited MDA-MB 231 (human breast adenocarcinoma) cells, with an IC(50) of 15 µg mL(-1), and the growth of Candida albicans, with an inhibition diameter of 18 mm, while its antioxidant activity, measured by DPPH and ABTS assay, proved to be negligible.

Essential oil from flowers (FL) and vegetative parts (VP) of Achillea ligustica (Asteraceae), naturalized after cultivation in central Italy, was investigated by GC–FID and GC–MS. The most abundant components were linalool, viridiflorol, β-pinene, 1,8-cineole and terpinen-4-ol. The antioxidant assays (DPPH and ABTS radical scavenging assays, and β -carotene bleaching test) demonstrated a moderate activity of essential oils. The antimicrobial activity was evaluated by the broth micro-dilution method on 6 microbial strains and showed to be quite strong against the cariogenic Gram-positive Streptococcus mutans , suggesting that this essential oil could be a valid candidate for anti-cariogenic formulations. Moderate cytotoxic activity was observed in assays on four tumour cell lines by MTT assay.

Wild pepper (Piper capense L.f., Piperaceae) is a spice traditionally used in western Cameroon to make soups called ‘ Nkui’ and ‘ Nah poh’. In the present work, the essential oil hydrodistilled from fruits was analyzed by GC-FID and GC-MS, and for in vitro biological activities, namely cytotoxic, antioxidant and antimicrobial, by MTT, DPPH, ABTS and agar disc diffusion methods. The oil composition was dominated by monoterpene hydrocarbons (56.5%) responsible for the pepper odor, such as β-pinene (33.2%), sabinene (10.0%) and α-pinene (8.9%). The oil induced a concentration-dependent inhibitory effect on human tumor cells MDA-MB 231 (breast adenocarcinoma), A375 (malignant melanoma) and HCT116 (colon carcinoma), showing IC50 values of 26.3, 76.0 and 22.7 μg/ml, respectively. The oil showed total antioxidant activity with a Trolox equivalent antioxidant concentration (TEAC) value of 140 μmol/g. The essential oil of P. capense proved to be an effective scavenger of the ABTS+ radical, with an activity only about 30 times lower than that of Trolox. Moderate activity was observed against the Gram-positive species Staphylococcos aureus and Enterococcus faecalis, and the yeast Candida albicans. The notable inhibition of some human tumor cells is worthy of further investigation to discover the possible mechanisms of action responsible for the observed cytotoxic effect of this essential oil.