OBJECTIVE

To investigate the chemical constituents of an endophytic fungus, Nodulisporium sp. A4, from the medicinal plant Aquilaria sinensis and search for antitumor natural products.

METHODS

The fungus was cultured in liquid medium and extracted with EtOAc. The compounds were isolated by various chromatographic methods (silica gel, reverse silica gel, Sephadex-LH20, preparative TLC and so on) and recrystallization. Structural elucidation was conducted by extensive analysis of spectroscopic data as well as by comparison with literature reports. The antitumor activity of isolated compounds was tested by MTT method in vitro.

RESULTS

Seven compounds were isolated and identified from the broth culture, their structures were determined to be 5-methyl-2-vinyltetrahydrofuran-3-ol (1), 6-methyl-2-(5-methyl-5-vinyltetrahydrofuran-2-yl) hept-5-en-2-ol (2), 6alpha-hydroxycyclonerolidol (3), rel-(1S,4S, 5R,7R,10R)-10-desmethyl-1-methyl-11-eudesmene (4), tyrosol (5), 8-methoxynaphthalen-1-ol (6), and 1,8-dimethoxynaphthalene (7). Three compounds were isolated and identified from the mycelia as ergosterol (8), ergosterol peroxide (9), and cerevisterol (10). The in vitro pharmalogical evaluation results displayed that compounds 3 and 4 showed 89.1%, 44.2% and 82.3%, 79.8% inhibition against tumor cell lines SF268 and NCI-H460 at 100 mg x L(-1), respectively.

CONCLUSIONS

Compound 1 was a new natural product, compounds 2, 3, 7 and 10 were reported from the genus Nodulisporium sp. for the first time. Compounds 3 and 4 exhibited weak inhibitory effects on the proliferation of tumor cell lines SF268 and NCI-H460.

To study the anti-tumor metastatic constituents in Rhodiola wallichiana (HK) S H Fu var Cholaensis (Praeg) S H Fu, chemical constituents were isolated and purified by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). Their structures were elucidated on the basis of spectral data analysis. The anti-tumor metastasis assay was applied to evaluate the activities of the isolated compounds. Ten compounds (1-10) were isolated and their structures were identified by comparison of their spectral data with literature as follows: syringic acid (1), salidroside (2), tyrosol (3), scaphopetalone (4), berchemol (5), 2,6-dimethoxyacetophenone (6), rhobupcyanoside A (7), miyaginin (8), chavicol-4-O-β-D-apiofuranosyl-(1 ->> 6)-O-β-D-glucopyranoside (9), eugenyol-O-β-D-apiofuranosyl-(1 ->> 6)-O-β-D-glucopyranoside (10). Compounds 4-6 and 8-10, were isolated from this genus for the first time, while compound 7 was isolated from this plant for the first time. Compounds 2, 6-8 showed positive anti-tumor metastatic activities, and compounds 2 and 8 showed significant anti-tumor metastatic activities.

Background: Phenolic compounds (polyphenols) are common plant secondary metabolites playing different roles in plants, and some of these vegetables and correlated fruits-figs, grapes, pomegranates, olives, date palms, etc.-contain remarkable and diversified amounts of these substances. In addition, polyphenols are reported to show positive effects for human health, because of their antioxidant behavior. Figs are an excellent source of polyphenols with highest concentrations of proanthocyanidins. Actually, figs contain higher amounts of polyphenols than red wine and tea.

Objective: Antioxidant activity of several flavonoids (a group of polyphenols) in figs is higher than that of, vitamin C, glutathione, or vitamin E. Pomegranates contain very high levels of polyphenols as compared to other fruits and vegetables. It is used in folklore medicine for the treatment of various diseases, such as hepatic damage, snakebite, ulcer, etc.

Method: The health-positive potential of pomegranate fruit has been mainly attributed to ellagitannins, the predominant class of phenolics in pomegoxidation.

Results: The chief phenolic compound found in fresh olive is the bitter secoiridoid oleuropein..

Conclusions: Processing of table olive decreases levels of oleuropein with correlated increases in the hydrolysis of hydroxytyrosol and tyrosol. Many of the health benefits reported for olives are thought to be associated with the levels of hydroxytyrosol. Date palm represents a staple food in most of the Arabian countries and is commonly consumed in several parts of the world.

Highlights: Numerous researches revealed the antibacterial, anti-hyperlipidemic, hepatoprotective, antimutagenic, and nephroprotective activity of date fruits, with reported anticancer and anti-fungal features.

Ethnopharmacological significance: Gmelina arborea Roxb.ex Smith, a fast-growing deciduous tree belongs to the family Lamiaceae, and is an important plantation species in many tropical areas around the world. The species is naturally distributed in semi-deciduous forests in tropical/subtropical regions of South East Asia. The tree is also an important medicinal plant in the Indian Systems of Medicine. The whole plant is used in medicine. It is astringent, bitter, digestive, cardiotonic, diuretic, laxative and pulmonary and nervine tonic. It improves digestion, memory, helps overcome giddiness and is useful in burning sensation, fever, thirst, emaciation, heart diseases, nervous disorders and piles. The roots are acrid, bitter-sweet in taste, stomachic, tonic, laxative, galactagogue and antihelmintic. The flowers are sweet, refrigerant, bitter, astringent and acrid, and are used in treating leprosy and skin diseases. The fruits are acrid, sour, sweet, refrigerant, bitter, astringent, aphrodisiac, trichogenous, alterant and tonic. Fruits are edible and also used for promoting hair growth and in treating anaemia, leprosy, ulcers, constipation, leucorrhoea and colitis. The leaves are a good fodder also. The major bioactive compounds extracted from different parts of G. arborea are arboreal, verbascoside, tyrosol, Iridoids, phenylpropanoid glycoside, premnazole, martynoside, iridoid glycosides, balanophonin, gmelinol, isoarboreol apig enin, umbelliferone etc. AIM OF THE REVIEW: This review provides an insight into the medicinal aspects of G. arborea. This review provides the latest information on phytochemistry, pharmacological activities and traditional uses of G.arborea.

Materials and methods: Information on G. arborea was gathered from various sources like textbooks, literature databases such as PubMed, Science Direct, Wiley, Springer, Taylor and Francis, Scopus, Inflibnet, Sci-Finder and Google Scholar.

Results: Sixty-nine phytochemicals which include lignans, acylated iridoid glycosides, acylated rhamnopyranoses, flavonoids, flavones, flavone glycosides have been isolated. Many of them have been characterized for their pharmacological activity. Several researchers have identified bioactive phytochemicals like luteolin, iridoid alkaloids from the leaves, hentriacontanol and lignans such as arboreol, isoarboreol, arborone, gmelanone, gummadiol from the heartwood, flavon glycosides in roots. The extracts are reported to have wound-healing and antidiarrheal properties. Various studies demonstrated that G.arborea and its constituents possess several pharmacological activities like anti-oxidant, anti-diabetic, anti-inflammatory, antiulcer, analgesic, anti-nociceptive, anticancer and wound healing activities.

Conclusion: G. arborea is a valuable medicinal plant used traditionally in the Indian Systems of Medicine (ISM - Ayurveda and Unani) to treat a wide variety of ailments. These phytochemicals are highly bioactive and exhibit various pharmacological activities. However, many compounds have been identified, whose pharmacological activities are yet to be understood.

Keywords: Gmelina arborea; Lamiaceae; pharmacological activities; phytochemistry; traditional uses.

Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from different regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed effects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (OR_{Q4 vs. Q1} = 0.47; 95% CI: 0.32-0.69 and OR_{Q4 vs. Q1} = 0.53; 95% CI: 0.36-0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (OR_{Q4 vs. Q1} = 0.41; 95% CI: 0.28-0.61), hydroxycoumarins (OR_{Q4 vs. Q1} = 0.49; 95% CI: 0.34-0.71), and tyrosols (OR_{Q4 vs. Q1} = 0.56; 95% CI: 0.39-0.80) were inversely associated with GC risk. No differences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results.

Keywords: MCC-Spain; anatomic; diet; epidemiology; gastric cancer; histologic; lignans; phenolic acids; polyphenols; stilbenes.

Oleuropein (Ole) is the main bioactive phenolic compound present in olive leaves, fruits and olive oil. This molecule has been shown to exert beneficial effects on several human pathological conditions. In particular, recent preclinical and observational studies have provided evidence that Ole exhibits chemo-preventive effects on different types of human tumors. Studies undertaken to elucidate the specific mechanisms underlying these effects have shown that this molecule may thwart several key steps of malignant progression, including tumor cell proliferation, survival, angiogenesis, invasion and metastasis, by modulating the expression and activity of several growth factors, cytokines, adhesion molecules and enzymes involved in these processes. Interestingly, experimental observations have highlighted the fact that most of these signalling molecules also appear to be actively involved in the homing and growth of disseminating cancer cells in bones and, ultimately, in the development of metastatic bone diseases. These findings, and the experimental and clinical data reporting the preventive activity of Ole on various pathological conditions associated with a bone loss, are indicative of a potential therapeutic role of this molecule in the prevention and treatment of cancer-related bone diseases. This paper provides a current overview regarding the molecular mechanisms and the experimental findings underpinning a possible clinical role of Ole in the prevention and development of cancer-related bone diseases.

Keywords: Bone; Cancer; Chemoprevention; Elenolic acid (PubChem CID: 169607); Hydroxytyrosol (PubChem CID: 82755); Metastasis; Oleuropein; Oleuropein (PubChem CID: 5281544); Oleuropein aglycone (PubChem CID: 56842347); Polyphenols; Tumor progression; Tyrosol (PubChem CID: 10393).

Olives affected by active and damaging infestation (olive fruit fly Bactrocera oleae (Rossi)) were assayed for their chemical composition. Biophenols were determined by HPLC, sterols, triterpenic dialcohols, and fatty acids by gas chromatography analysis. The acquired data were statistically analyzed. Oils produced from "Istrska belica" fruit affected by active infestation compared to the oils made from fruit affected by damaging infestation showed higher amounts of total oleuropein biofenols (377.3 versus (vs.) 106.6 mg/kg), total biophenols (755 vs. 377 mg/kg), lignans (85.3 vs. 32.9 mg/kg), the dialdehydic form of decarboxymethyl oleuropein aglycone (DMO-Agl-dA) (148.3 vs. 49.0 mg/kg), its oxidized form (DMO-Agl-dA)ox (35.2 vs. 8.5 mg/kg), the dialdehydic form of oleuropein aglycone (O-Agl-dA) (61.1 vs. 8.0 mg/kg), the dialdehydic form of ligstroside aglycone (L-Agl-dA) (63.5 vs. 28.0 mg/kg), the aldehydic form of oleuropein aglycone (O-Agl-A) (40.6 vs. 8.4 mg/kg), and lower amounts of tyrosol (Tyr) (6.0 vs. 13. 9 mg/kg) and the aldehydic form of ligstroside aglycone (L-Agl-A) (13.8 vs. 40.3 mg/kg). Higher values of stigmasterol (2.99%) and lower values of campesterol (2.25%) were determined in oils affected by damaging infestation; an increase in triterpenic dialcohols was also observed (3.04% for damaging and 1.62% for active infestation). Oils affected by damaging infestation, compared to active infestation, showed lower amounts of oleic acid (73.89 vs. 75.15%) and higher amounts of myristic (0.013 vs. 0.011%), linoleic (7.27 vs. 6.48%), and linolenic (0.74 vs. 0.61%) acids.

Keywords: biophenols; fatty acids; olive fruit fly; sterols; triterpenic dialcohols; “Istrska belica”.

From the chloroform part of Ligustrum delavayanum Hariot, leaves five constituents were isolated: tyrosol, esculetine, kempferol-7-O-rhamnoside, quercetine-3-O-glucoside, and quercetine. Further six constituents (probably malvidine, two secoiridoid glycosides, caffeic acid monosaccharide ester, quercetine monoglycoside (no hyperoside), and quercetine diglycoside (no rutinoside)) were isolated from the methanolic part of above mentioned drug.

The compound 3,4,5-trihydroxy-N-[2-p-tolylethyl]-benzamide (THTEB) is one of the derivatives of tyrosol, which is p-tyrosol combined with gallic acid by an amide bond. In this study, THTEB displayed a significant antiproliferative effect on human cervical carcinoma (HeLa) cells. Cell cycle analysis revealed that THTEB could arrest HeLa cells in the S phase with a concomitant decrease in the cells' G0/G1 and G2/M phases. According to the [3H]thymidine incorporation assay results, we found that THTEB could inhibit DNA replication, which suggests that THTEB-induced S phase arrest might be the direct result of blocked DNA synthesis. However, THTEB had very weak effect on replication protein A (RPA)'s ssDNA binding activity and the topoisomerase I (topo I)-mediated DNA relaxation activity, signifying that RPA and topo I were not the main target molecules in the inhibition of DNA replication. Furthermore, by using alkaline single-cell gel electrophoresis (comet assay), we found severe DNA damage caused by THTEB. In conclusion, these results suggest that THTEB could induce tumor cell antiproliferation correlated with DNA damage and DNA replication inhibition, but the target molecule of THTEB remains elusive.

An endophytic fungus Talaronyces pinpurogenus was isolated from the seeds of the popular edible fruit Pouteria campechiana. The fungus was fermented in potato dextrose agar and the fungal media were extracted with EtOAc. Chromatographic separation of the EtOAc extracts over silica gel, Sephadex LH-20 and preparative thin layer chromatography furnished a furanone analogue of talaroconvolutin A, named talarofuranone (1), along with talaroconvolutin A (2), 4-hydroxyactophenone, tyrosol and ergosterol. The structure of 1 was determined by comparing the NMR data with that of 2 and by HRFABMS.

Different grades of genuine and counterfeit Fraxinus excelsior exudates, marketed as natural sweeteners or mild laxatives, were evaluated for their proximate composition and for saccharidic, organic acids, lipidic and phenolic profile by means of GC-MS and (1)H NMR. Genuine samples contained mannitol (39-48 g/100 g, according to the grade), fructose (9-16 g/100 g), glucose (2-3.7 g/100 g), sorbitol (0,5-0,6 g/100 g), galactose (0.02-0.74 g/100 g), oligosaccharides as mannotriose (13-22 g/100 g) and stachyose (1-11 g/100 g), and traces of myo-inositol, mannose, sucrose. On the contrary, counterfeit samples contained mostly mannitol and sorbitol, with traces of fructose, glucose and mannose. Differences in ash, total polyphenolic content and fatty acid composition allowed a quick identification of counterfeit products, confirmed by a distinct mono-, oligosaccharidic and phenolic pattern. Elenolic acid (63-1628 mg/kg), tyrosol (15-774 mg/kg), homovanillic acid (2,39-52.8 mg/Kg), dopaol (0.8-63 mg/kg), pinoresinol (4.2-18.5 mg/kg) and fraxetin (0.25-11.64 mg/kg), albeit showing a wide concentration range, were the most abundant substances detected in the phenolic fraction of Fraxinus manna, while esculetin, p-hydroxybenzoic acid, 4-hydroxyphenacetic acid, 3,4 hydroxybenzoic acid, hydroxy-pinoresinol, medioresinol and siringaresinol were present in low amounts. The polyphenolic profile may be used as a marker for authentication and should be considered in the evaluation of nutritional and health properties ascribed to Fraxinus manna.

Pulp-enriched powder (POPP) was obtained from olive pomace solid fraction, a derived from the new value chain established for olive by-products. As a multifunctional powder, POPP retains several bioactive compounds (fatty acids, dietary fibre and phenolics) under potential synergic interaction, even more, reactive throughout the digestion. So, in this study, the potential multifunctionality of POPP was evaluated after the gastrointestinal tract. A significant loss of phenolics occurred during oral digestion (62.48%). However, the potential role of dietary fibre as phenolics' carrier and its possible liberation in the stomach allowed recovering a significant amount of phenolics (77.11%) and a bioaccessibility index of at least 50% (mainly for tyrosol and its glucoside). POPP also provides high content of dietary fibre mainly insoluble fibre (69.68 g/100 g dry weight) linked to a substantial amount of bound phenolics (7.63 mg of gallic acid equivalents/g fibre dry weight), with a positive effect on the fatty acids bioaccessibility [decreased the saturated (5-6%) and facilitated the unsaturated fatty acids bioaccessibility (4-11%)]. PCA analysis became evident the negative effect of simulated gastrointestinal digestion upon POPP as mainly linked to phenolics' loss. Despite all negative effects of the simulated digestion on POPP bioactive composition, phenolics and unsaturated fatty acids showed to be bioaccessible in significant amount, and the amount of bound phenolics associated to fibre retained in the colon have the potential to exert gut health benefits.

Keywords: Antioxidant dietary fibre; In vitro digestion; Multifunctional powder; Olive pomace.

Olive oil is an important product in the Mediterranean diet, due to its health benefits and sensorial characteristics. Picholine marocaine is the most cultivated variety in Morocco. The present research aims to evaluate the phenolic compounds, vitamin E and fatty acids of commercial Picholine marocaine virgin olive oils (VOOs) from five different North Moroccan provinces (Chefchaouen, Taounate, Errachidia, Beni Mellal and Taza), using HPLC-photodiode array (PDA)/electrospray ionization (ESI)-MS, normal phase (NP)-HPLC/ fluorescence detector (FLD) and GC-flame ionization detector (FID)/MS, respectively. The obtained results showed an average content of 130.0 mg kg^-1 of secoiridoids (oleuropein aglycone, 10-hydroxy-oleuropein aglycone and ligstroside aglycone, oleocanthal and oleacein), 108.1 mg kg^-1 of phenolic alcohols (tyrosol and hydroxytyrosol), 34.7 mg kg^-1 of phenolic acids (caffeic acid, ferulic acid and elenolic acid), and 8.24 mg kg^-1 of flavonoids (luteolin, luteolin glucoside, apigenin). With regard to vitamin E, α-tocopherol was the most abundant vitamin E (57.9 mg kg^-1), followed by α-tocotrienol (2.5 mg kg^-1), γ-tocopherol (4.5 mg kg^-1) and β-tocopherol (1.9 mg kg^-1), while δ-tocopherol was not detected. Moreover, 14 fatty acids were found and, among them, oleic acid (76.1%), linoleic acid (8.1%) palmitic acid (8.7%) and stearic acid (2.5%) were the major fatty acids detected. Finally, heat map and principal component analysis allowed us to classify the studied provinces in terms of VOO chemical composition: Chefchaouen (tyrosol and hydroxytyrosol), Taounate (oleuropein aglycone), Errachidia (ferulic acid, w-3 and w-6), Beni Mellal (oleocanthal) and Taza (luteolin and oleic acid).

Keywords: GC-FID/MS; HPLC-PDA/ESI-MS; NP-HPLC/FLD; Picholine marocaine; fatty acids; phenolic compounds; virgin olive oils; vitamin E.

The study was conducted to determine the effects of cultivar, harvest period and their interaction on the hydrophilic phenolic components extra virgin olive oils of the cultivars 'Ayvalık', 'Memecik' and 'Topakaşı'. Olives were collected at three different harvesting periods; (1) early harvest period-1 (Beginning of spotting), (2) early harvest period-2 (End of spotting), and (3) optimum harvest period. Oils were extracted using an abencor system. HPLC (High-performance liquid chromatograph) technique was used to quantify The phenolic compounds including: tyrosol (p-HPEA), hydroxytyrosol (3,4-DHPEA), luteolin, rutin, quercetin, catechin, sinapinic acid, p-coumaric acid, cinnamic acid, vanillin, vanillic acid, ferulic acid and gallic acid were quantified using HPLC. The results indicated that the effects of harvest period on the phenolic components were variety dependent. At the early harvest period-1, 'Memecik' and 'Topakaşı' had the highest efficiency in luteolin, cinnamic acid, vanillic acid, and ferulic acid contents, while 'Ayvalık' had the highest efficiency in hydroxytyrosol, sinapinic acid, p-coumaric, vanillin and ferulic acid contents. At the optimum harvest period, 'Ayvalık' had the highest efficiency in luteolin, tyrosol and gallic acid contents, while 'Topakaşı' had the highest efficiency in tyrosol, hydroxytyrosol and rutin content. The highest phenolic content was detected in the early harvest period-1. The content of tyrosol linearly increased with the progress of maturity harvest period, whereas the contents of the sinapinic acid, vanillin, vanilic acid and ferulic acid decreased. The oils of 'Memecik' variety had significantly higher phenolic content than those of 'Ayvalık' and 'Topakaşı' varieties.

Keywords: Cultivars; Hydroxytyrosol; Maturity stage; Olive oil; Phenolic; Tyrosol.

Caffeic acid phenethyl ester (CAPE) is an ester of a hydroxycinnamic acid (phenylpropanoid) and a phenylethanoid (2-phenylethanol; 2-PE), which has long been used in traditional medicine. Here, we synthesized 54 hydroxycinnamic acid-phenylethanoid esters by feeding 64 combinations of hydroxycinnamic acids and phenylethanols to Escherichia coli harboring the rice genes OsPMT and Os4CL. The same approach was applied for ester synthesis with caffeic acid and eight different phenyl alcohols. Two hydroxycinnamoyl phenethyl esters, p-coumaroyl tyrosol and CAPE, were also synthesized from glucose using engineered E. coli by introducing genes for the synthesis of substrates. Consequently, we synthesized approximately 393.4 mg/L p-coumaroyl tyrosol and 23.8 mg/L CAPE with this approach. Overall, these findings demonstrate that the rice PMT and 4CL proteins can be used for the synthesis of diverse hydroxycinnamoyl phenylethanoid esters owing to their promiscuity and that further exploration of the biological activities of these compounds is warranted.

The experiments performed on emotional--painful stress model in rats demonstrated cardioprotective activity of adaptogens of vegetable origin (rodiolae, eleutherococcus, levsea, p-tyrosol). Preliminary injection of rodiolae extract was found to prevent stress--induced increase in cAMP level and cGMP content decrease in heart. We can conclude that adaptogens cardioprotective effect may be the drugs to prevent stressor change in cyclic nucleotides level in myocardium.

The effect of red and white wine total extracts and phenolic fractions on heat shock protein (Hsp) levels in tumor cells and on tumor and endothelial cell populations in vitro has been investigated. Total extracts of red wines decreased Hsp70 and Hsp27 levels and the numbers of tumor and endothelial cells. Several red and white wine fractions significantly decreased Hsp27 levels, and some of them had also an effect on Hsp70 levels. A red wine fraction rich in polymeric flavanols and a white wine one rich in phenolic acids, flavonols, and tyrosol strongly lowered Hsp27 levels. Some red and white wine fractions strongly reduced tumor cell numbers, whereas most of them decreased endothelial cell numbers to variable extents. The present results indicate that wine phenolics decrease Hsp levels in tumor cells and tumor and endothelial cell populations. These properties may be important in the potent anticarcinogenic action of wine phenolics.

A simple, sensitive and fast responding device is described for the discrimination of hydrophilic ortho-diphenols, whose presence in abundant enough amounts is typical for extra virgin olive oils (EVOOs), from hydrophilic mono-phenols instead present in almost all vegetable oils. It consists of a dual electrode detector pencil-drawn at the end of a paper microfluidic channel, defined by hydrophobic barriers, where samples of these antioxidants, extracted from vegetable oils by a 80:20% v/v acetonitrile/water mixture, were applied. Thin-layer chromatographic runs conducted by using a 0.01 M H2SO4 + 1 M KCl running buffer allowed the selective detection of hydrophilic ortho-diphenols by profiting from the fact that they undergo reversible oxidation at less positive potentials than those required by monophenols for displaying their irreversible anodic process. On this basis, a potential for the oxidation of hydrophilic ortho-diphenols was applied to the upstream pencil-drawn electrode (W1) (at which a minor fraction of mono-phenols was also oxidized), while a potential for the reverse process involving the sole product (ortho-quinones) of the reversible oxidation of ortho-diphenols was imposed at the downstream pencil-drawn working electrode (W2). Thus, cathodic peak currents linearly dependent on analyte concentrations could be recorded at W2 which led to a satisfactory detection limit (8 μM, equivalent to 1.23 mg/L) even when working electrodes W1 and W2 with same dimensions were employed. Improved sensitivities and lower detection limits were achieved by increasing the dimensions of W2 with respect to W1, thanks to the improvement of the collection efficiency. Throughout this investigation, hydroxytyrosol (HTy) and tyrosol (Ty) were adopted as models of ortho-diphenols and mono-phenols, respectively, in view of their abundant presence in EVOOs. Real samples of EVOO from different production companies, of a simple olive oil and of a sunflower oil were analyzed. Different hydrophilic ortho-diphenol contents were found in EVOO samples (up to 40.8 mg/kg), while only a negligible amount turned out to be present in simple olive oil. No trace of these antioxidants were instead found in sunflower oil, as expected. All concentrations found were in good agreement with those detected by a more frequently employed spectrophotometric method used for the sake of comparison.

Considering the growing number of extra virgin olive oil (EVOO) producers in the world, knowing the influence of olive oils with different geographical origins on the characteristics of the final blend becomes an interesting goal. The present work is focused on commercial organic EVOO blends obtained by mixing multiple oils from different geographical origins. These blends have been studied by ¹H-NMR spectroscopy supported by multivariate statistical analysis. Specific characteristics of commercial organic EVOO blends originated by mixing oils from Italy, Tunisia, Portugal, Spain, and Greece were found to be associated with the increasing content of the Italian component. A linear progression of the metabolic profile defined characteristics for the analysed samples-up to a plateau level-was found in relation to the content of the main constituent of the Italian oil, the monocultivar Coratina. The Italian constituent percentage appears to be correlated with the fatty acids (oleic) and the polyphenols (tyrosol, hydroxytyrosol, and derivatives) content as major and minor components respectively. These results, which highlight important economic aspects, also show the utility of ¹H-NMR associated with chemometric analysis as a powerful tool in this field. Mixing oils of different national origins, to obtain blends with specific characteristics, could be profitably controlled by this methodology.

Keywords: 1H-NMR spectroscopy; extra virgin olive oil; multivariate statistical analysis; traceability.

Endophytic fungi are biodiverse and alternative source of bioactive compounds, due their different abilities of genetic expression and alteration of biosynthetic pathway when submitted to different culture conditions. The metabolic profile of three different crude extracts (A, B and C), obtained from the endophytic fungus Asordaria conoidea, were evaluated by HPLC and ¹H NMR. Antioxidant and allelochemical activity were also evaluated. OSMAC diversified the metabolic production, mainly in the solid culture, where the tyrosol, 4-hydroxybenzaldehyde, 2-phenylacetamide and vanillic acid were isolated. The structures of the compounds were elucidated mainly by NMR. Extracts had antioxidant potential, however, only Extract C showed allelochemical activity, as inhibition of 65.5% in growth. This study confirms the efficiency of the OSMAC platform in producing extracts of different properties and compounds. Herein the A. conoidea was isolated for the first time as an endophytic microorganism.

Keywords: Cochlospermum regium; Endophytic fungus; allelochemical activity; aromatic compounds; fungi metabolism.

Maturity is one of the most important factors associated with the quality of olive products, however the molecular events underlying olive drupe development remain poorly characterized. Using proteomic and metabolomic approaches, this study investigated the changes in the olive drupes (cv. Chondrolia Chalkidikis) across six developmental stages (S1-S6) that characterize the dynamics of fruit growth and color. Primary metabolites, including carbohydrates and organic acids (i.e., xylose, malic acid), showed significant accumulation in the black maturation stage. Temporal changes in various secondary metabolites (e.g., oleuropein, oleacin and tyrosol) were also observed. Proteins involved in oxidation-reduction (i.e., LOX1/5), carbohydrate metabolism (i.e., GLUA, PG) and photosynthesis (i.e., chlorophyll a-b binding proteins) significantly altered in the turning black compared to the green mature stage. By providing the first proteometabolomic study of olive drupe development, this investigation offers a novel framework for further studies on this economically relevant crop.

Keywords: Maturity; Olive drupe development; Primary metabolism; Proteomics; Secondary metabolism.

Curcumin is a bioactive natural compound with a wide range of pharmacological properties, including antitumor activity; however, its clinical application has been limited because of its low solubility, stability, and bioavailability. In this study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics of curcumin in good purity and yield. The non-effective findings in pancreatic cancer cells switched to strong growth inhibition and cell death efficacy for PC3 prostate cancer cells, and mimic 9, in which tyrosol (TYR) and homovanillyl alcohol (HVA) units were linked by a phosphodiester bond, was quite effective not only in cell growth inhibition but also in causing strong cell death under the study conditions and treatments that were not effective in PANC1 cells. The results got more exciting when we also consider the findings in SW480 human colorectal carcinoma cell line, where the growth inhibitor effects were more in line with that of the PC3 cells, but the lack of cell death effect was more in line with the PANC1 cells.

Keywords: Colorectal cancer; Curcumin mimics; Pancreatic cancer; Prostate cancer; Solid phase synthesis.

A detailed phytochemical investigation of the leaves of the Australian rainforest tree Eupomatia laurina, led to the discovery of five new neolignans, eupomatenes A - E and eight known compounds, eupomatenoid-2, trans-(2'S)-2-[1'-(4-methoxyphenyl)prop-2'-yl]anethol, chlorogenic acid, chlorogenic acid-methyl ester, tyrosol-1-O-β-xylopyranosyl-1(1 → 6)-O-β-glucopyranoside, leucoside, kaempferol-3-O-neohesperidoside, and pachypodol. The structures of all the compounds were determined by detailed spectroscopic analysis. All compounds were also evaluated for their anti-inflammatory properties by assessing their inhibitory effects on nitric oxide (NO) production and TNF- α release in RAW 264.7 macrophages. Whilst slight anti-inflammatory activity (in terms of inhibition of NO production) was observed with eupomatenes A - E, this was also associated with high levels of cell growth inhibition.

Keywords: Anti-inflammatory; Eupomatia; Neolignans; Nitric oxide.

Adulterations of food and pharmaceutical preparations are the important global problem. On the one hand, fraud practices are becoming more and more sophisticated while on the other, monitoring and uncovering falsifications are insufficient. One of the most common consumer concern is the quality and authenticity of the purchased products, related to the confidence that they have composition and properties in accordance with the manufacturer's declaration on the label. This refers also to pharmaceuticals potentially delivering great health benefits such as Rhodiola rosea L. supplements. The aim of this study was defining authenticity and possible adulterations of two R. rosea preparations basing on their TLC-bioprofiles and the presence of biomarker compounds characteristic for this plant. The effect-directed analysis (EDA), i.e. TLC hyphenated with micro-chemical and biological assays performed directly on TLC plates followed by HPLC-ESI-MS was used for the bioprofiling of antioxidants, antibacterials, and inhibitors of lipase, acetylcholine, α-glucosidase and tyrosinase as well as for the identification of the biomarkers. The results pointed to the possible adulteration of one of the tested products related to the absence of two rosavins, the most important quality markers of R. rosea.

Keywords: Authenticity; Effect-directed analysis; Rhodiola rosea L.; Rosavins; Salidroside; p-Tyrosol.