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Objective Carpobrotus edulis (L.) N.E.Br. is a succulent perennial plant native to South Africa and grows invasively in the Mediterranean basin. It is commonly used for the treatment of various diseases, including skin wound healing and regeneration, for which experimental validation is lacking. We therefore evaluated the skin healing properties by testing a C. edulis aqueous leaf extract (CAE) on cell cultures and in enzymatic assays. Methods Micro-morphological analysis of leaves was carried out using scanning electron microscopy and light microscopy. Phytochemical features and antioxidant activity of CAE were evaluated by reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS), and in vitro cell-free assays. Biological activities were evaluated using keratinocytes and fibroblasts, as well as elastase, collagenase, and hyaluronidase. Results CAE showed high carbohydrates (28.59% ± 0.68%), total phenols ([101.9 ± 6.0] g gallic acid equivalents/kg dry extract [DE]), and flavonoids ([545.9 ± 26.0] g rutin equivalents/kg DE). RP-LC-DAD-ESI-MS revealed the predominant presence of hydroxycinnamic acids (51.96%), followed by tannins (14.82%) and flavonols (11.32%). The extract was not cytotoxic, had a strong and dose-dependent antioxidant activity, and inhibited collagenase (> 90% at 500 µg/mL) and hyaluronidase (100% at 1000 µg/mL). In cell culture experiments, CAE increased wound closure and collagen production, which was consistent with its high polyphenol content. Conclusion Our data support the use of the C. edulis for skin care and the treatment of skin problems. Moreover, use of C. edulis for skin care purposes could be an eco-friendly solution to reduce its invasiveness in the environment.

The aim of the present study has been to evaluate the antioxidant, antimicrobial and wound healing activity of Algerian Lavandula stoechas and Mentha pulegium methanol extracts (LE and ME, respecti...

Citrus lumia Risso Essential oil Antioxidant properties Anti-cholinesterase activity Cytotoxicity Neuroactive effects 1. Introduction Plants that produce essential oils (EOs) represent a large part of natural flora and an important resource in various fields such as pharmaceutical, food and cosmetic industries, due to their flavor, fra- grance and biological activity (Swamy et al., 2016). EOs play a pivotal role in the growth and colonization of plants, giving color and scent to reproductive organs, attracting pollinators, favoring seed dispersion (Sharifi-Rad et al., 2017), and defending the plant against abiotic (light, temperature, etc.) and biotics (herbivores, harmful insects and pa- thogen microbes) stressors (Sharifi-Rad et al., 2017). More than 250 types of essential oils are commercialized annually on the international market, some of which are used since ancient times in popular medi- cines (Jarić et al., 2015; Mahboubi, 2015), in aromatherapy, and as a therapeutic aid in the treatment of various pathologies including car- diovascular and neurological diseases, as well as diabetes and cancer (Swamy et al., 2016; Lillehei and Halcon, 2014; Solórzano-Santos and ABSTRACT The use of essential oils (EOs) is known since long time in traditional medicine and aromatherapy for the management of various oxidative stress-related disorders and has been further increased recently for their neuroprotective and anti-aging potentials as well as for reducing anxiety and stress. The purpose of this work was to evaluate, for the first time, the chemical composition of Citrus lumia Risso EO and its antioxidant, anti-cholinesterase, and neuroactive properties by cell-free and cell-based assays. The EO has shown strong antioxidant and free radical scavenging properties, particularly in hydrogen atom transfer based assays (β-carotene bleaching and ORAC, IC50 22 μg/mL and 46 μg/mL, respectively), that can be attributed to the high content of monoterpenes, especially D-Limonene (48.905%), and Linalool (18.245%). Furthermore, the EO has shown an interesting anti-acetylcholinesterase activity (IC50 258.25 μg/mL). Data from MTT analysis indicate that the cytotoxicity of EO, evaluated on L929 mouse fibroblasts, is very low, with an IC50 higher than 500 μg/mL at 48 h. Rat neuronal networks subjected to EO showed a concentration-dependent in- hibition of spontaneous electrical activity. Results indicate that C. lumia EO could be an important source of natural antioxidants suggesting an im- portant preventive role in the onset of oxidative stress-related pathologies.

Background: Inflammatory bowel diseases (IBD), mainly Ulcerative colitis (UC) and Crohn’s disease (CD), are recurrent idiopathic non-infectious chronic diseases widely diffused worldwide and characterized by moderate to severe mucosal damage. Objective: The aim of this study was to review the literature of the last 10 years to photograph pre-clinical and clinical data on the use of nutraceuticals in the prevention and treatment, also combined with the conventional drugs, of IBD. Method: PubMed, MEDLINE, Embase, Web of Science and ClinicalTrials.gov were used for searching the most recent publications on in vitro, in vivo and clinical evidences on IBD and nutraceuticals by assessing the originality and scientific rigor of studies. Results: In the last decade, the interest in new healthy or therapeutic complementary or alternative approaches to conventional drugs in IBD has grown inexorably, as well as the incidence of these pathologies and the knowledge on their etiopathogenesis. In this context, a growing development of new nutraceutical products with a consequent increase in pre-clinical studies has been observed. However, this panorama does not yet translate into adequate clinical studies that can effectively endorse what was observed in preclinical studies, many of them are mostly aimed at resolving diseases related to IBD rather than IBD itself. Conclusion: Despite the promising preclinical data about nutraceuticals and IBD, we are still very far from being able to postulate an adequate nutraceutical treatment of these pathologies and further studies are necessary to support this hypothesis.

Viral infections represent one of the main causes of disease worldwide, especially today due to the increase of migration, global travel, and urbanization. The several side effects of the conventional drugs and the growing phenomenon of resistance have led researchers to turn to the plant kingdom as a source of potential new antiviral drugs. The aim of this work is to summarize the updated evidence for antiviral activity of different plants and their isolated bioactive compounds, evaluating also the potential interactions, which can occur in cotreatment with conventional antiviral drugs. The plant complexes have proved to be usually more active than their most abundant isolated compounds by hypothesizing synergistic mechanisms. In addition to cellular and molecular investigations, molecular docking studies have proved essential in highlighting the interaction mechanisms of bioactive compounds with target molecules. However, the use of nonstandardized extracts, or too high concentrations in vitro, which do not reproduce their bioavailability in vivo, are often limiting factors. Moreover, the lack of studies concerning the safety profile of plant extracts and their isolated compounds, alone or in combination with conventional antiviral drugs, is the most worrying aspect. In light of this, further studies are needed to validate their possible therapeutic use.

Atopic dermatitis is a multifactorial immune-mediated skin disorder characterized by an alteration of epidermal barrier function and onset of skin lesions, which range from mild erythema to severe lichenification. Treatment consists in hydration with possible use of topical or immunomodulatory corticosteroids, which, however sometimes showed side effects. Recently, the interest in natural compounds has grown significantly and among these, hydroxytyrosol (HT) plays a pivotal role due to its strong and well-known anti-inflammatory activity.The aim of this study was to investigate the safety and efficacy of Fenolia® Eudermal Cream 15 (HT-based formulation) on epidermal barrier impaired as consequence of skin injury.Whit this purpose, morphologic and structural as well as anti-inflammatory evaluations, after treatment with pro-inflammatory mediators (PBS 1 X and LPS) and HT-based formulation on reconstructed human epidermis (RHE) were carried out by qualitative (hematoxylin/eosin- and immunostaining) and quantitative (MTT assay, IL-1α and IL-8 release by ELISA) techniques. Furthermore, HT absorption through the epidermal barrier was evaluated by RP-LC-DAD analysis.A rise in the thickness of the epidermis as well as an appropriate maturation and protein expression (Loricrin, Fillagrin, E-Cadherin and Cytokeratins 56) were detected in treated RHE samples. In particular, the HT-based formulation was found to stimulate cell proliferation, as evidenced by the significant increase in Ki67 expression, which suggests the involvement of repair mechanisms, increasing epithelial regeneration and differentiation and improving the epidermal barrier effect. Furthermore, HT-based formulation showed a statistically significant anti-inflammatory activity by reducing both IL-1α and IL-8 release by RHE tissues, greater than the reference drug dexamethasone. Finally, excellent transcutaneous absorption values were found for HT, demonstrating how this new formulation increases the availability of the bioactive compound.In light of these results, Fenolia® Eudermal Cream 15 could be an effective agent to counteract atopic dermatitis. Graphical abstract Safety and efficacy of hydroxytyrosol-based formulation on skin inflammation: in vitro evaluation on reconstructed human epidermis model.

The aim of this work was to investigate the phytochemical profile and biological properties of different colours of betalain cactus pear extracts, evaluating their antioxidant, cytoprotective, and anti-angiogenic properties by cell-free, cell-based, and in vivo assays. A QuEChERS extraction method followed by RP-LC-DAD-MS/MS analysis showed that indicaxanthin and betanin were the main compounds (≥94.32% and ≥96.95%, respectively). Orange cactus pear extracts exert the best antioxidant activity in all assays carried out, in particular into ORAC (17,352.55 ± 987.407 mg trolox equivalents/100 g dry weight) and β-carotene bleaching (60.35%) assays. The red ones, instead, showed the best cytoprotective activity decreasing the cell mortality, LDH, and Caspase-3 release ranging from 4.0 to 55%. According to antioxidant results, the orange cactus pear extracts showing also the highest anti-angiogenic activity (IC50 19.31 μg/ml), followed by the red (IC50 23.55 μg/ml) and the yellow ones (IC50 33.97 μg/ml). In light of the results and correlation analysis, the behaviour of these molecules varies a lot according to their structure and physicochemical features and synergistic activity between betalain classes may be postulated; so the plant complex could be of greater interest compared with the isolated molecules for potential nutraceutical and pharmaceutical uses.

Euphorbia dendroides L. is a rounded shrub commonly found in the Mediterranean area well-known, since ancient times, for its traditional use. The aim of the present study was to investigate the phytochemical profile as well as the antioxidant and anti-inflammatory properties of flower (FE), leaf (LE), fruit (FrE), and branch (BE) hydroalcoholic extracts. For this purpose, a preliminary phytochemical screening followed by RP-LC-DAD-ESI-MS analysis, as well as several in vitro cell-free colorimetric assays, were carried out. Moreover, the toxicity of the extracts was investigated by the brine shrimp lethality assay. All extracts showed a high content of polyphenols, in particular phenolic acids (chlorogenic acid 0.74–13.80 g/100 g) and flavonoids (rutin 0.05–2.76 g/100 g and isovitexin 8.02 in BE). All the extracts showed strong and concentration-dependent antioxidant and anti-inflammatory activity with, on average, the following order of potency: FE, LE, FrE, and BE. Interestingly, all the extracts investigated did not show any toxicity on Artemia salina. Moreover, the only LD50 found (BE, 8.82 mg/mL) is well above the concentration range, which has been shown the biological properties. Considering this, this study offers the first evidence of the possible use of the polyphenol extracts from the aerial parts of E. dendroides as promising antioxidant and anti-inflammatory agents.

In the present study an acidified methanol pistachio hull extract was investigated for antioxidant and inhibitory effects on melanin biosynthesis by in vitro and in vivo assays. The chromatographic analysis revealed that cyanidin-3-O-galactoside represents the main compound (98.37%). The pistachio hull extract efficiently inhibits the mono and diphenolase activity of mushroom tyrosinase (IC50= 141.07 and 116.08 μg/mL, respectively) and it was able, thanks to its strong antioxidant and free-radical scavenging activities, to hinder the l-DOPA auto-oxidation in a concentration-dependent manner (125–500 μg/mL). Results of in vivo assay showed that the treatment with pistachio hull extract (10 μg/mL) reduced pigmentation in zebrafish embryos at early stages of development (60.01% of inhibition vs control). In conclusion, these findings suggest that the ripe pistachio hull may be considered as a promising source of antioxidant and skin whitening agents for the development of new products useful in preventing the pigmentation disorders in humans and/or to improve the food quality.

The aim of the study was to investigate the micromorphology of Mentha pulegium leaves and flowers harvested in three different Sicilian (Italy) areas with peculiar pedo-climatic conditions, and to characterize the phytochemical profile, the phytotoxic activity, and the eco-compatibility of their essential oils (EOs) for potential use as safe bioherbicides. Light microscopy (LM) and scanning electron microscopy (SEM) highlighted that M. pulegium indumentum consists of non-glandular and glandular trichomes of different types. Peltate trichomes of plants from the different sites showed few significant differences in dimension and abundance, but they were characterized by a surprisingly high number of secretory cells both in leaves and flowers. Phytochemical analyses showed that oxygenated monoterpenes were the most abundant class in all the EOs investigated (92.2–97.7%), but two different chemotypes, pulegone/isomenthone and piperitone/isomenthone, were found. The complex of morphological and phytochemical data indicates that soil salinity strongly affects the expression of the toxic metabolite pulegone, rather than the EO yield. Phytotoxicity tests showed a moderate activity of EOs against the selected species as confirmed by α-amylase assay. Moreover, the low toxicity on brine shrimp provided a rationale for the possible use of investigated EOs as eco-friendly herbicides.

The aim of study was to validate, by in vitro and in vivo studies, the traditional use for wound-healing activity of Artemisia absinthium L. Reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS) analysis allowed to identify eleven polyphenols with chlorogenic acid as the most abundant compound (3.75 g/100 g of dry extract). After that, antibacterial activity as well as acute dermal and oral toxicity were assessed in animal models. In order to investigate the wound-healing activity of A. absinthium methanol extract, two ointments were formulated (MEO 5% and 10%). The ointment with the highest concentration of plant extract (10%) showed a statistically significant effect on the rats wound contraction, similar to that exerted by the reference drug Cicatryl-Bio. Moreover, A. absinthium methanol extract showed the best antibacterial activity against the Gram-negative Escherichia coli ATCC 10536 (MIC 1.25&ndash, 2.5 mg/mL) and the Gram-positive Staphylococcus aureus ATCC 6538 (0.31&ndash, 0.625 mg/mL). The absence of oral and topical toxicity of the treated animals allowed to establish the safety of the ointments. Overall, data collected in the present study support and validate the use of A. absinthium as a wound healing agent in the Algerian traditional medicine.

The essential oils (EOs) of the Eurasiatic Valeriana officinalis (Vo), the Himalayan Valeriana jatamansi (Vj) and Nardostachys jatamansi (Nj), are traditionally used to treat neurological disorders. A multidisciplinary approach based on micromorphology, DNA barcoding, EOs characterization as well as evaluation of the biological effects on the nervous system was carried out. Nj showed the highest inhibitory activity on acetylcholinesterase (IC50 67.15 μg/mL), followed by Vo (IC50 127.30 μg/mL) and Vj (IC50 246.84 μg/mL). Microelectrode arrays analyses on rat cortical neurons revealed stronger inhibition by Nj (IC50 18.8 and 11.1 μg/mL) and Vo (16.5 and 22.5 μg/mL), compared with Vj (68.5 and 89.3 μg/mL). These results could be related to the different EOs composition and in particular to the different content of oxygenated compounds such as aldehydes and ketones, which represents a discriminating factor in determining the order of potency. In conclusion, this multidisciplinary approach could be a useful tool to quickly discriminate these three plant species and avoid adulterations.

Background: Almond kernels contain phytochemicals with positive health effects in relation to heart disease, diabetes and obesity. Several studies have previously highlighted that almond cell wall encapsulation during digestion and particle size are factors associated with these benefits. In the present study, we have characterized almond oleosomes, natural oil droplets abundant in plants, and we have investigated their integrity during simulated gastrointestinal digestion. Methods: Oleosomes were visualized on the almond seed surface by imaging mass spectrometry analysis, and then characterized in terms of droplet size distribution by dynamic light scattering and protein profile by liquid chromatography high-resolution tandem mass spectrometry analysis. Results: The almond oleosomes&rsquo, distribution remained monomodal after in vitro mastication, whereas gastric and duodenal digestion led to a bimodal distribution, albeit characterized mainly by a prevalent population with a droplet size decrease related to a rearrangement of the protein profile. Oleosins, structural proteins found in plant oil bodies, persisted unchanged during simulated mastication, with the appearance of new prunin isoforms after gastric and duodenal digestion. Conclusions: The rearrangement of the protein profile could limit lipid bioaccessibility. The data improve our understanding of the behavior of almond lipids during gastrointestinal digestion, and may have implications for energy intake and satiety imparted by almonds.

The aim of the study was to investigate the absorption and transport mechanisms as well as the anti-inflammatory properties of ideain on Caco-2 transwell model. A concentration and time-dependent bidirectional transport was highlighted; despite this, a clear saturation of the transepithelial absorption in the A-B direction was observed at ideain concentration > 10 μM, suggesting an involvement of membrane transporters. Comparing Papp and PDR values of ideain (10 μM) to reference drugs with a low to a high apparent permeability, it is possible to predict a low in vivo absorption, with a transport efficiency of 1.03%. Co-treatments with several EDTA-Na2 concentrations (1–5 mM) and P-gp inhibition studies with verapamil 100 μM ruled out a passive diffusion of this molecule as well the possibility that P-gp could affect ideain absorption. Inhibition studies using 2 mM phloridzin (SGLT1 inhibitor) and 2 mM phloretin (GLUT2 inhibitor), showed a clear SGLT1 and GLUT2 involvement in the ideain absorption, with SGLT1, which plays the pivotal role. Finally, preliminary anti-inflammatory studies showed that ideain is able to modulate, at a pharmanutritional dose, and with a comparable activity in respect to the reference drug dexamethasone (10 μM), the LPS-induced inflammation in Caco-2 transwell model, which makes it a potentially useful molecule for nutraceutical purpose.

Himantoglossum robertianum (Loisel.) P. Delforge is a Mediterranean orchid whose propagation in vitro has been achieved, making it eligible as a source of bioactive substances. Flowers were analyzed by light and SEM microscopy and used to obtain a polyphenol-rich, hydroalcoholic flower extract (HFE). HFE was characterized for total phenols, flavonoids and proanthocyanidins, and for polyphenol profile by RP-LC-DAD. Antioxidant assays, in vitro collagenase and elastase inhibition, and MTT and cell motility assays on HaCaT keratinocytes were done. Microscopy showed epidermal cells containing anthocyanins in the flower labellum. Flavonoids (flavones and flavan-3-ols) represented the most abundant compounds (42.91%), followed by scopoletin (33.79%), and phenolic acids (23.3%). Antioxidant assays showed strong activities, rating ORAC > FRAP > TEAC > β-carotene bleaching > DPPH > iron-chelation. Biological assays showed elastase and collagenase inhibition (up to 42% and 78%, respectively), improvement of HaCaT cell viability after treatment with 500 μM H2O2 (from 30% to 84% of control), and stimulation of cell migration rate up to 210% of control. In summary, HFE counteracted different free radicals, while protective properties were shown by cell-free and cell-based bioassays, suggesting the possible use of H. robertianum flowers for skin-preserving, repair, and anti-aging applications.

The aim of this study was to compare the micro-morphological features of two different non-drug Cannabis sativa L. biotypes (Chinese accession G-309 and one fibrante variety) and to evaluate the phytochemical profile as well as some biological properties of the essential oils (EOs) obtained by hydrodistillation of dried flowering tops. After a micro-morphological evaluation by scanning electron microscopy, the phytochemical composition was analysed by GC-FID and GC-MS analyses. Antioxidant and anti-acetylcholinesterase properties were investigated by several in vitro cell-free assays, while neuroactive effects were evaluated on mouse cortical neuronal as well as human iPS cell-derived central nervous system cells grown on MEA chips. Both EOs showed strong antioxidant properties mainly attributable to the high content of hydroxylated compounds as well as significant anti-acetylcholinesterase activities (IC50 74.64 and 57.31 μg/ml for Chinese accession and fibrante variety, respectively). Furthermore, they showed a concentration-dependent inhibition of spontaneous electrical activity of human and mouse neuronal networks, with the fibrante variety, which showed the best activity (MFR, IC50 0.71 and 10.60 μg/ml, respectively). The observed biological activities could be due to a synergic effect between terpenes and phytocannabinoids, although in vivo studies, which clarify the molecular mechanism, are still lacking.

Acca sellowiana (O. Berg) Burret (Feijoa) is an evergreen shrub, belonging to the Mirtaceae family. The aim of this study was to investigate the micromorphological features of the feijoa fruit peel and to evaluate the phytochemical profile, as well as the antioxidant, cytoprotective, and antimicrobial properties of its essential oil (EO), by several in vitro cell-free and cell-based assays. The micromorphological analysis showed several schizogenic secretory cavities, immediately below the epidermal layer. Forty compounds were identified and quantified by GC-FID and GC-MS analyses. Sesquiterpenes were the most abundant ones (76.89%), followed by monoterpene hydrocarbons (3.26%), and oxygenated monoterpenes (0.34%). The main compounds were &gamma, Selinene (17.39%), &alpha, Cariophyllene (16.74%), &beta, Cariophyllene (10.37%), and Germacene D (5.32%). The EO showed a strong and dose-dependent antioxidant, and free-radical scavenging activity. Furthermore, it showed cytoprotective activity on the lymphocytes, that have been pre-treated with 100 &mu, M tert-butyl-hydroperoxide (t-BOOH), as well as a decrease in intracellular reactive oxygen species (ROS), induced by t-BOOH on erythrocytes. A preliminary antimicrobial screening against GRAM+ and GRAM&minus, bacteria, as well as on fungi highlighted that EO showed the best activity against S. aureus and C. albicans (MIC 2.7 mg/mL). In light of these results, feijoa fruit EO could find various applications, especially in the food, nutraceutical, and pharmaceutical fields.

The genus Alnus (Betulaceae) comprises many species with a long history in traditional medicines. The crude extracts and isolated compounds from Alnus species exhibit a wide spectrum of in vitro and in vivo pharmacological activities (1). Phytochemical investigations revealed the presence of diarylheptanoids, a class of natural products typically found in Alnus genus with two aryl groups joined by a heptane chain in the main skeleton that have drawn attention due to their multiple biological properties and their therapeutic potential (2). A previous study reported that oregonin and other structurally analogous diarylheptanoids isolated from the bark of A. hirsuta showed inhibitory effects on melanogenesis in B16 melanoma cells.(3). Nowadays the discovery of new whitening agents from natural sources is increasing, due to the weak effectiveness and unwanted side effects of currently available compounds. In this context, the aim of this study was to evaluate the skin whitening capabilities of crude extracts (80% aqueous MeOH) obtained from the fresh bark of Alnus glutinosa (L.) Gaertn. and Alnus cordata (Loisel) Duby, an endemic species in the Mediterranean areas (4). As tyrosinase is the rate-limiting enzyme in melanin biosynthesis, the inhibitory effects of A. glutinosa and A. cordata extracts (AGE and ACE, respectively) on mushroom tyrosinase activity were preliminary evaluated. In addition, the anti-melanogenic ability of AGE and ACE was further investigated on the pigmentation of early stage zebrafish at 72 hours post fertilization (hpf) to find new skin whitening agents without cytotoxic concerns. Results of the enzymatic assay showed that ACE was capable to inhibit dose dependently L-DOPA oxidation catalyzed by tyrosinase (IC50 = 77.44 ± 0.54 μg/mL) as compared to the reference inhibitor kojic acid (2.24 ± 0.18 μg/mL). Unlike, AGE exhibited a lower anti-tyrosinase activity (100 μg/mL reached 28% of inhibition while higher doses showed pro-oxidative effects). Moreover, the zebrafish in vivo assay revealed that ACE (50 μg/mL) has equivalent inhibitory effects on the pigmentation (76.57%) to that of phenylthiourea (PTU, 30 μg/mL), used as the reference inhibitor (77.80%), as compared to control, while they did not affect the embryos development and survival. Conversely, the depigmenting effects of AGE were about 10 fold less than ACE (45.28% at 500 μg/mL). A mild anti-melanogenic activity was also evidenced for the diarylheptanoid oregonin (10% of inhibition at 20 μg/mL). A preliminary phytochemical screening evidenced that ACE and AGE have a high phenolic content (399.27 ± 14.30 and 534.17 ± 20.60 mg GAE/g of extract, respectively). However, despite AGE showed the highest phenolic content, the quali-quantitative RP-HPLC-DAD analysis highlighted as it is predominantly composed by oregonin (418.45 μg/mg of AGE vs 1.23 μg/mg of ACE) that exhibited a mild anti-melanogenic activity both in vitro and in vivo assays. Further phytochemical investigations are still in progress to identify the bioactive compounds of ACE as to be considered a potential candidate for the treatment of skin disorders due to its bleaching properties and favorable safety profiles.

Background:Isoflavones are naturally occurring flavonoids, commonly found in the food consumed for centuries in the East-Asian population, characterized by a structure able to exert nonsteroidal estrogen-like activity on human cells. They have attracted researcher interest all around the word, following the results obtained in epidemiological and clinical studies. The involvement of isoflavones and their metabolites in various biological processes suggests that they can influence several metabolic pathways and can influence the gene expression at epigenetic level, involving effects that probably are due to early life exposure. They show positive health effects on several diseases, especially in the prevention of coronary heart and neurological diseases, hormone-related cancers, osteoporosis, and postmenopausal symptoms.Methods:We have performed a critical evaluation of available literature trough a structured search of bibliographic databases about isoflavones health promoting properties, risk assessment and mechanisms of action. In addition, we supplied useful information on their biochemical properties, sources and bioavailability.Results:Although these molecules have been the subjects of numerous researches, their role for the wellness of the human organism remains controversial. Moreover, there are substantial inconsistencies between the results obtained by epidemiologic studies conducted on Eastern population, which found high health promoting properties, and Western clinical trials, which found much less positive effects.Conclusion:Further epidemiologic studies and well-designed prospective human studies are to determine the beneficial effects of isoflavones exposure, as well as establishing its safe therapeutic.

Drug performance in the gastrointestinal tract (GIT) plays a crucial role in determining release and absorption. In the present work, we assessed the in vitro digestion of two synthetic N1-aryl-2-arylthioacetamidobenzimidazoles (NAABs), NAAB-496 and NAAB-503, using bio-relevant models of the human stomach and small intestine. The activity of NAAB-496 and NAAB-503 against herpes simplex virus (HSV-1) replication was also investigated. NAAB-496 was resistant to pepsin in the gastric environment, with a virtual 100% recovery, which decreased to 43.2% in the small intestine. NAAB-503 was sensitive to pepsin, with 65.7% degradation after 120 min gastric phase. 1H Nuclear magnetic resonance (NMR) post in vitro digestion highlighted an alteration of NAAB-496 after the gastric phase, whereas NAAB-503 appeared comparable to the original spectral data. Both NAAB-496 and NAAB-503 revealed some antiviral activity anti-HSV-1. The 50% effective concentration (EC50) of the compounds was 0.058 mg/mL for NAAB-496 and 0.066 for NAAB-503. Future studies will evaluate the behavior of NAAB-496 within pharmaceutical formulations.

Citrus fruits are a rich source of bio-functional compounds with various and well-proven health properties. We focused our attention on an ancient Mediterranean species, Citrus lumia Risso. The aim of this work was to investigate the polyphenol content and biological activities of C. lumia albedo extract by cell-free and cell-based assays. Fifteen polyphenols were quantified by LC-DAD-FLD analysis (flavonoids 89.34% and phenolic acids 10.66%) with eriocitrin and hesperidin as major components (52.81% and 31.31%, respectively). These results were corroborated also by micromorphological observations, which showed clusters of needle-shaped crystals of hesperidin highlighted by TBO staining. C. lumia albedo extract revealed marked antioxidant and free radical scavenging properties, and a significant cytoprotective activity on t-BOOH-treated lymphocytes. Results indicate that C. lumia albedo extract could be exploited as an antioxidant source, suggesting the use of albedo, currently considered a by-product, as a valuable raw material for nutraceutical employments.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Several studies suggest that the improvement of oxidative stress is suggested as a possible therapeutic strategy for pediatric nonalcoholic steatohepatitis. We performed a randomized, double-blind placebo-controlled trial to test the potential efficacy, assessed by improvement of oxidative stress parameters and liver ultrasound, and tolerability of a mixture of vitamin E and hydroxytyrosol (HXT) in adolescents with biopsy-proven NAFLD. Four hundred forty consecutive patients were screened, 80 of these with biopsy-proven NAFLD were enrolled. Forty patients received an oral dose of HXT and vitamin E and 40 children received the capsules of placebo for 4 months. Seventy patients completed the study. Patients in the treatment arm showed a decrease of insulin resistance (IR), triglyceride levels, oxidative stress parameters, and steatosis grade. Noteworthy, the steatosis improvement correlates with the levels of advanced glycation end products and carbonylated proteins. The HXT and vitamin E treatment improved the main oxidative stress parameters, IR, and steatosis in children with NAFLD. The use of two natural molecules that may have antioxidant effects seems a promising strategy that could be easily diet integrated to improve NAFLD-related liver damage in children.

In this study, we investigated the phenolic composition of the crude extract (MeOH 80 %) of Alnus cordata (Loisel.) Duby stem bark (ACE) and its antioxidant and skin whitening properties. RP-LC-DAD analysis showed a high content of hydroxycinnamic acids (47.64 %), flavanones (26.74 %) and diarylheptanoids (17.69 %). Furthermore, ACE exhibited a dose-dependent antioxidant and free-radical scavenging activity, expressed as half-maximal inhibitory concentration (IC50 ): Oxygen radical absorbance capacity (ORAC, IC50 1.78 μg mL-1 )>Trolox equivalent antioxidant capacity (TEAC, IC50 3.47 μg mL-1 )>2,2-Diphenyl-1-picrylhydrazyl (DPPH, IC50 5.83 μg mL-1 )>β-carotene bleaching (IC50 11.58 μg mL-1 )>Ferric reducing antioxidant power (FRAP, IC50 17.28 μg mL-1 ). Moreover, ACE was able to inhibit in vitro tyrosinase activity (IC50 77.44 μg mL-1 ), l-DOPA auto-oxidation (IC50 39.58 μg mL-1 ) and in an in vivo model it exhibited bleaching effects on the pigmentation of zebrafish embryos (72 h post fertilization) without affecting their development and survival. In conclusion, results show that A. cordata stem bark may be considered a potential source of agents for the treatment of skin disorders due to its bleaching properties and favorable safety profiles, associated to a good antioxidant power.

Today, in many European countries, people are looking for wild edible plants to experience new tastes and flavors, by following the new trend of being green and environmentally friendly. Young borage and spinach leaves can be easily confused by inexpert pickers with those of other plants, including poisonous ones, such as Mandragora autumnalis Bertol. (mandrake) or Digitalis purpurea L. (foxglove), common in southern and northern Italy respectively. In the last twenty years, several cases of intoxication by accidental ingestion of mandrake and foxglove have been reported. The purpose of this work was to perform a pharmacognostic characterization of young leaves from borage, mandrake, foxglove and spinach, by micro-morphological, molecular and phytochemical techniques. The results showed that each of the three techniques investigated could be sufficient alone to provide useful information for the identification of poisonous species helping the medical staff to manage quickly the poisoned patients. However, the multi-disciplinary approach proposed could be very useful to asses the presence of poisonous plants in complex matrices, to build a database containing morphological, molecular and phytochemical data for the identification of poisonous species or in forensic toxicology, given their increasingly frequent use due to their low cost and relatively common availability.

Black carrot (Daucus carota L. ssp. sativus var. atrorubens Alef.) is a valuable source of carbohydrates, minerals and vitamins and contains also high amounts of anthocyanins giving the characteristic deep-purple color. These latter compounds are known as natural dyes used in the food and pharmaceutical industry that have recently attracted much attention for their healthful properties. The aim of this work was to investigate for the first time the polyphenolic profile and biological properties of a black carrot crude extract (BCCE) through an in-depth analysis of the main polyphenolic classes evaluating its antioxidant, cytoprotective and anti-angiogenic properties. Twenty five polyphenols were quantified by LC-DAD-FLD-MS/MS analysis (anthocyanins 78.06%, phenolic acids 17.89% and other flavonoids 4.06%) with polyglycosylated cyanidins as major components. In addition, BCCE showed a strong antioxidant and free radical scavenging activity particularly in the hydrogen transfer-based assays (ORAC and β-carotene bleaching) and a significant increase in the cell viability. Furthermore, BCCE exhibited a strong anti-angiogenic activity at the highest concentration assayed on the chick chorioallantoic membrane (50μg/egg). In conclusion, the obtained results demonstrated the antioxidant, cytoprotective and anti-angiogenic properties of BCCE, which highlight that the higher biological activity of BCCE is probably due to the synergic effects exerted by various polyphenolic classes.

Although the chemical composition and biological properties of some species of the genus Pistacia has been investigated, studies on hull essential oil of Pistacia vera L. variety Bronte (HEO) are currently lacking. In this work, we have carried out an in-depth phytochemical profile elucidation by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, and an evaluation of antioxidant scavenging properties of HEO, using several different in vitro methods, checking also its cytoprotective potential on lymphocytes treated with tert-butyl hydroperoxide. Moreover, the antimicrobial activity against Gram-positive and Gram-negative strains, both American Type Culture Collection (ATCC) and clinical isolates, was also investigated. GC-MS analysis highlighted the richness of this complex matrix, with the identification of 40 derivatives. The major components identified were 4-Carene (31.743%), α-Pinene (23.584%), d-Limonene (8.002%), and 3-Carene (7.731%). The HEO showed a strong iron chelating activity and was found to be markedly active against hydroxyl radical, while scarce effects were found against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Moreover, pre-treatment with HEO was observed to significantly increase the cell viability, decreasing the lactate dehydrogenase (LDH) release. HEO was bactericidal against all the tested strains at the concentration of 7.11 mg/mL, with the exception of Pseudomonas aeruginosa ATCC 9027. The obtained results demonstrate the strong free-radical scavenging activity of HEO along with remarkable cytoprotective and antimicrobial properties.

Phytochemicals are non-nutrient bioactive compounds occurring in plants and food, which possess the capacity to modulate one or more metabolic processes or pathways in the body, resulting to health benefits and promotion of well-being. The interest of the scientific community continues to grow, powered by progressive research efforts to identify properties and potential applications of bioactive substances, and coupled with public interest and consumer demand. However, the natural derivation of these compounds is not a feature of harmlessness, over that of therapeutic efficacy, to which is also added the absence of post-marketing monitoring which does not allow to evaluate the occurrence of adverse effects related to the use of their related products. The literature is particularly rich of studies concerning phytochemicals as environmental estrogens, which result in infertility, reproductive abnormalities, and tumors but also in some endocrine-related health effects. Nevertheless, further studies have been performed to better understand the bioavailability, pharmacokinetics and mode of action of these compounds which seems to go beyond their ability to bind to oestrogen receptors and either stimulate or inhibit the activity of endogenous oestrogens, highlighting new interesting target molecules and signaling pathways. The present review summarizes the latest developments and knowledge concerning the assessment of endocrine activities of dietary phytochemicals focusing on pharmacological aspects.