Search

The SARS-CoV-2 pandemic has caused approximately 6.3 million deaths, mainly due to the acute respiratory distress syndrome or multi-organ failure that characterizes COVID-19 acute disease. Post-acute COVID-19 syndrome, also known as long-COVID, is a condition characterized by a complex of symptoms that affects 10-20% of the individuals who have recovered from the infection. Scientific and clinical evidence demonstrates that long-COVID can develop in both adults and children. It has been hypothesized that multi-organ effects of long-COVID could be associated with the persistence of virus RNA/proteins in host cells, but the real mechanism remains to be elucidated. Therefore, we sought to determine the effects of the exogenous expression of the papain-like protease (PLpro) domain of the non-structural protein (NSP3) of SARS-CoV-2 in polarized human airway (Calu-3), intestinal (Caco-2), and liver (HepG2) epithelial cells, and to evaluate the ability of the natural antioxidant hydroxytyrosol (HXT) in neutralizing these effects. Our results demonstrated that PLpro was able to induce a cascade of inflammatory genes and proteins (mainly associated with the interferon pathway) and increase the apoptotic rate and expression of several oxidative stress markers in all evaluated epithelial cells. Noteably, the treatment with 10 μM HXT reverted PL-pro-dependent effects almost completely. This study provides the first evidence that SARS-CoV-2 PLpro remaining in host cells after viral clearance may contribute to the pathogenetic mechanisms of long-COVID. These effects may be counteracted by natural antioxidants. Further clinical and experimental studies are necessary to confirm this hypothesis.

This study evaluated the micro-morphology as well as the chemical and biological features of Citrus lumia seeds. The cream-colored pyriform seed showed a woody coat covered by a thick layer of mucilage and an embryo with two large cotyledons rich in oil bodies. Hydroxycinnamic acid glycosides and flavonoids are the most abundant compounds in methanol and ethyl acetate extracts (ME and EAE), respectively. Conversely, fatty acids and α-tocopherol represent the main bioactive compounds in the hexane extract (HE). ME showed the most promising antioxidant and anti-inflammatory activities already in cell-free assays. These results were confirmed by experiments carried out on human primary cells. Indeed, ME showed the best inhibitory activity against heat-induced haemolysis and ROS formation in erythrocytes. Moreover, the same order of potency (ME > EAE > HE) was observed also on peripheral blood mononuclear cells, in which the seed extracts were able to decrease TNF-α and IL-6 release after LPS-induced inflammation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recipes on the composition of the "salad of the monks" (Capuchin monks) have been reported in Italy since the 17th century. Different wild edible plants were highly regarded as an important ingredient of this mixed salad. Among these, some species played a key role for both their taste and nutritional properties: Plantago coronopus L. (PC), Rumex acetosa L., Cichorium intybus L., and Artemisia dracunculus L. In the present study, the micromorphological and phytochemical features as well as the antioxidant and anti-inflammatory properties of extracts of these fresh and blanched leaves, were investigated. The extracts obtained by blanched leaves, according to the traditionally used cooking method, showed the highest content of bioactive compounds (total phenols 1202.31-10,751.88 mg GAE/100 g DW; flavonoids 2921.38-61,141.83 mg QE/100 g DW; flavanols 17.47-685.52 mg CE/100 g DW; proanthocyanidins 2.83-16.33 mg CyE/100 g DW; total chlorophyll 0.84-1.09 mg/g FW; carbohydrates 0.14-1.92 g/100 g FW) and possess the most marked antioxidant (IC 50 0.30-425.20 µg/mL) and anti-inflammatory activity (IC 50 240.20-970.02 µg/mL). Considering this, our results indicate that increased consumption of the investigated plants, in particular of PC, raw or cooked briefly, could provide a healthy food source in the modern diet by the recovery and enhancement of ancient ingredients.

Most of traditional knowledge about plants and their uses is fast disappearing because of socio-economic and land use changes. This trend is also occurring in bio-cultural refugia, such as mountain areas. New data on Traditional Ethnobotanical Knowledge (TEK) of Italian alpine regions were collected relating to three valleys (Cogne, Valsavarenche, Rhêmes) of the Gran Paradiso National Park. Extensive dialogues and semi-structured interviews with 68 native informants (30 men, 38 women; mean age 70) were carried out between 2017 and 2019. A total of 3918 reports were collected, concerning 217 taxa (including 10 mushrooms, 1 lichen) mainly used for medicinal (42%) and food (33%) purposes. Minor uses were related to liquor making (7%), domestic (7%), veterinary (5%), forage (4%), cosmetic (1%) and other (2%). Medicinal plants were used to treat 14 ailment categories, of which the most important were respiratory (22%), digestive (19%), skin (13%), musculoskeletal (10%) and genitourinary (10%) diseases. Data were also evaluated by quantitative ethnobotanical indexes. The results show a rich and alive traditional knowledge concerning plants uses in the Gran Paradiso National Park. Plants resources may provide new opportunities from the scientific point of view, for the valorization of local products for health community and for sustainable land management.

Edible flowers are attracting special therapeutic attention and their administration is on the rise. Edible flowers play pivotal modulatory roles on oxidative stress and related interconnected apoptotic/inflammatory pathways toward the treatment of cancer. In this review, we highlighted the phytochemical content and therapeutic applications of edible flowers, as well as their modulatory potential on the oxidative stress pathways and apoptotic/inflammatory mediators, resulting in anticancer effects. Edible flowers are promising sources of phytochemicals (e.g., phenolic compounds, carotenoids, terpenoids) with several therapeutic effects. They possess anti-inflammatory, anti-diabetic, anti-microbial, anti-depressant, anxiolytic, anti-obesity, cardioprotective, and neuroprotective effects. Edible flowers potentially modulate oxidative stress by targeting erythroid nuclear transcription factor-2/extracellular signal-regulated kinase/mitogen-activated protein kinase (Nrf2/ERK/MAPK), reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA) and antioxidant response elements (AREs). As the interconnected pathways to oxidative stress, inflammatory mediators, including tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukins (ILs) as well as apoptotic pathways such as Bcl-2-associated X protein (Bax), Bcl-2, caspase and cytochrome C are critical targets of edible flowers in combating cancer. In this regard, edible flowers could play promising anticancer effects by targeting oxidative stress and downstream dysregulated pathways.

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., (Copyright © 2021 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

The aim of study was to evaluate and compare the phytochemical profile, the antioxidant and antimicrobial properties of two standardized extracts from non-psychotropic (Δ 9 -tetrahydrocannabinol ≤0.2%) Cannabis sativa L. var. fibrante rich in cannabidiol (CBD). The two extracts, namely Cannabis Fibrante Hexane Extract 1 (CFHE1) and Cannabis Fibrante Hexane Extract 2 (CFHE2), were obtained by extraction with acidified hexane from dried flowering tops as such and after hydrodistillation of the essential oil, respectively. Gas chromatographic analysis showed that cannabinoids remained the predominant class of compounds in both extracts (82.56% and 86.38%, respectively), whereas a marked depletion of the terpenes occurred. Moreover, liquid chromatographic analysis highlighted a high titer of cannabidiol acid (CBDA) and CBD in CFHE1 and CFHE2, respectively. Both extracts showed a strong and concentration-dependent antioxidant activity and a potent antimicrobial activity against both Staphylococcus aureus ATCC 6538 (MIC and MBC of 4.88 μg/ml for CFHE1, and 4.88 and 19.53 μg/ml, respectively, for CFHE2) and methicillin resistant clinical strains (MIC values between 1.22 and 9.77 μg/ml and MBC values between 4.88 and 78.13 μg/ml). Considering this, the obtained results suggest that standardized extracts of C. sativa var. fibrante could find promising applications as novel antimicrobial agents., (© 2021 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Background: The rise in paediatric non-alcoholic fatty liver disease (NAFLD) is particularly alarming. We recently reported that Hydroxytyrosol (HXT) and Vitamin E (VitE) may improve oxidative stress, insulin resistance, and steatosis in children with biopsy-proven NAFLD., Aim: Here, we investigated if HXT+VitE may reduce systemic inflammation in the above-mentioned patients., Methods: This study analysed the plasma levels of IL (interleukin)-6, IL-1β, IL-10, tumour necrosis factor (TNF)-α, 4‑hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'deoxyguanosine (8-OHdG) in children enrolled in the HXT+VitE trial (ClinicalTrials.gov, NCT02842567)., Results: Changes in markers of systemic inflammation were found in both placebo (Pla) and HXT+VitE. In particular, after four months, the levels of IL-1β and TNF-α were reduced in both groups, while IL-6 decreased, and IL-10 increased significantly only in the group treated with HXT+VitE. Children treated with HXT+VitE showed a significant decrease of 4-HNE and 8-OHdG that correlated with the improvement of triglyceride levels. Noticeably, only the 8-OHdG decrease correlated with steatosis amelioration and with the increase of IL-10 levels., Conclusion: The treatment with HXT and VitE reduced the NAFLD-related systemic inflammation in children, mainly by an increase of IL-10 circulating levels that occurred in response to DNA damage recovery, ultimately improving steatosis and hypertriglyceridemia., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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 LD 50 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.

Genistein is an isoflavone first isolated from the brooming plant Dyer's Genista tinctoria L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword "genistein" from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Javad Sharifi-Rad et al.)

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 (IC 50 = 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.

Recently, several studies have highlighted the role of Citrus flavanones in counteracting oxidative stress and inflammatory response in bowel diseases. The aim of study was to identify the most promising Citrus flavanones by a preliminary antioxidant and anti-inflammatory screening by in vitro cell-free assays, and then to mix the most powerful ones in equimolar ratio in order to investigate a potential synergistic activity. The obtained flavanones mix (FM) was then subjected to in vitro simulated digestion to evaluate the availability of the parent compounds at the intestinal level. Finally, the anti-inflammatory activity was investigated on a Caco-2 cell-based model stimulated with interleukin (IL)-1β. FM showed stronger antioxidant and anti-inflammatory activity with respect to the single flavanones, demonstrating the occurrence of synergistic activity. The LC-DAD-ESI-MS/MS analysis of gastric and duodenal digested FM (DFM) showed that all compounds remained unchanged at the end of digestion. As proof, a superimposable behavior was observed between FM and DFM in the anti-inflammatory assay carried out on Caco-2 cells. Indeed, it was observed that both FM and DFM decreased the IL-6, IL-8, and nitric oxide (NO) release similarly to the reference anti-inflammatory drug dexamethasone.

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 1.25-2.5 mg/mL) and the Gram-positive Staphylococcus aureus ATCC 6538 (0.31-0.625 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.

Citrus juices are a rich source of bioactive compounds with various and well-known health benefits. The aim of this study was to investigate the polyphenols and ascorbic acid content as well as to investigate the antioxidant, anti-inflammatory and anti-angiogenic properties of the juice of an ancient Mediterranean species, Citrus lumia Risso (CLJ). The antioxidant and anti-inflammatory activities were evaluated by several in vitro cell-free and cell-based assays, whereas two different in vivo models, the chick chorioallantoic membrane (CAM) and the zebrafish embryos, were used to characterize the anti-angiogenic properties. Twenty-eight polyphenols were identified by RP-LC-DAD-ESI-MS analysis (flavonoids 68.82% and phenolic acids 31.18%) with 1-caffeoyl-5-feruloylquinic acid and kaempferol 3'-rhamnoside, which represent the most abundant compounds (25.70 and 23.12%, respectively). HPLC-DAD analysis showed a high ascorbic acid content (352 mg/kg of CLJ), which contributes with polyphenols to the marked and dose-dependent antioxidant and anti-inflammatory properties observed. CLJ showed strong and dose-dependent anti-angiogenic activity as highlighted by the inhibition of blood vessel formation on CAMs and the decrease of endogenous alkaline phosphatase on zebrafish embryos. Moreover, within the concentration range tested, no dead or malformed embryos were recorded. Certainly, further studies are needed to investigate the molecular mechanisms underlying these promising biological effects, but considering the evidence of the present study, the use of CLJ as a ready-to drink safe prevention strategy for inflammatory-based diseases correlated to angiogenesis could be justified., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Smeriglio, Denaro, D’Angelo, Germanò and Trombetta.)

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' 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-Na 2 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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The potential efficacy of selected plant extracts to counteract the dermal toxicity of jellyfish envenomation was investigated using an in vitro cell culture model., Methods: We studied plant extracts from Carica papaya, Ananas comosus, and Bouvardia ternifolia, known for their antivenom properties, in pairwise combinations with tissue homogenates of the jellyfish Pelagia noctiluca, Phyllorhiza punctata, and Cassiopea andromeda, to evaluate modulations of jellyfish cytotoxic effects. L929 mouse fibroblasts were incubated with pairwise jellyfish/plant extract combinations and examined by MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide)., Results: C papaya and A comosus significantly lowered the cytotoxicity of P noctiluca and P punctata but induced a slight worsening of C andromeda cytotoxicity. Conversely, B ternifolia was protective against P punctata, ineffective against P noctiluca, and worsened C andromeda cytotoxicity., Conclusions: Data showed species-specific and contrasting effects of plant extracts, suggesting that those containing protease activities, namely A comosus and C papaya, are more effective in lowering the cytotoxicity of jellyfish venom containing toxic peptidic factors such as phospholipase A. However, all examined plants require further investigation in vivo to evaluate their ability to counteract jellyfish injury to the skin., (Copyright © 2020 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Lemon bottlebrush ( Callistemon citrinus (Curtis) Skeels) is one of the most common ornamental plants, diffused worldwide, and characterized by the presence of flowers with an intense red/purple coloration. There is increasing interest in the use and application of anthocyanins for their unique structural/chemical features in both food and pharmaceutical applications. RP-HPLC-DAD-ESI-MS/MS analysis of an enriched fraction of acidified methanolic extract of C. citrinus flowers allow the possibility of identifying, for the first time, the presence of four anthocyanins: cyanidin-3,5- O -diglucoside (cyanin), peonidin-3,5- O -diglucoside (peonin), cyanidin-3- O -glucoside, and cyanidin-coumaroylglucoside-pyruvic acid. Moreover, the evaluation of antioxidant and biological potential showed a remarkable activity of this fraction, able to actively scavenge DPPH, AAPH, and ABTS radicals, and to counteract the β-carotene-bleaching. In addition, it protects human mononuclear cells from oxidative injuries and prevents angiogenesis (acting in the range of few μg/ml); furthermore, it does not show significant iron-chelating ability (up to 200 µg/mL). The easy way of cultivation, robustness, and adaptability to different environments make the flowers of this plant a useful source of anthocyanins, with remarkable health promoting properties.

The essential oils (EOs) of three Caprifoliaceae species, the Eurasiatic Valeriana officinalis (Vo), the Himalayan Valeriana jatamansi (Vj) and Nardostachys jatamansi (Nj), are traditionally used to treat neurological disorders. Roots/rhizomes micromorphology, DNA barcoding and EOs phytochemical characterization were carried out, while biological effects on the nervous system were assessed by acetylcholinesterase (AChE) inhibitory activity and microelectrode arrays (MEA). Nj showed the highest inhibitory activity on AChE (IC 50 67.15 μg/mL) followed by Vo (IC 50 127.30 μg/mL) and Vj (IC 50 246.84 μg/mL). MEA analyses on rat cortical neurons, carried out by recording mean firing rate (MFR) and mean bursting rate (MBR), revealed stronger inhibition by Nj (IC 50 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 different EO compositions, since sesquiterpenes and monoterpenes significantly contribute to the observed effects, but the presence of oxygenated compounds such as aldehydes and ketones is a discriminating factor in determining the order of potency. Our multidisciplinary approach represents an important tool to avoid the adulteration of herbal drugs and permits the evaluation of the effectiveness of EOs that could be used for a wide range of therapeutic applications.

The aim of this study was to characterize the chemical composition and to evaluate the antimicrobial and phytotoxic properties of the essential oils (EOs) obtained from leaves of Leptospermum petersonii chemotype "Variety B" and Eucalyptus gunnii , native to Australia. Geranyl acetate, γ-terpinene, geraniol, terpinolene, α-pinene, p -cimene, and linalool were the main components in L. petersonii EO, confirming also the existence of several chemotypes in such taxa; on the other hand, 1,8-cineole, trans -sabinene hydrate acetate, globulol, longicyclene, terpinolene, and camphene were present in major amounts in the E. gunnii EO. Chemical analysis of L. petersonii revealed that it belongs to the variety "B." E. gunnii EO showed good antibacterial activity, with an MIC of 0.5 and 2 μg/mL against Staphylococcus aureus , and Pectobacterium carotovorum , respectively. The activity of E. gunnii EO was stronger than L. petersonii EO, whose maximum MIC reached 5 μg/mL. E. gunnii and L. petersonii EOs were particularly effective in inhibiting the biofilm formation by S. aureus , already at a concentration of 0.01 μg/mL. The other strains were resistant to both EOs up to a dose of 0.05 μg/mL. The maximum inhibition on biofilm formed by P. carotovorum was recorded for E. gunnii EO, reaching a value of 93.12% at 1.0 μg/mL. This is the first manuscript which studies the biofilm inhibition by EOs and evaluates their effects on biofilm metabolism. Both EOs were more effective against P. carotovorum . In addition, even though L. petersonii EO 0.1 μg/mL was unable to inhibit biofilm formation by Escherichia coli , it decreased the metabolic activity of the biofilm to 78.55% compared to control; furthermore, despite it inducing a relatively low inhibition (66.67%) on biofilm formation, it markedly affected metabolic activity, which decreased to 16.09% with respect to the control. On the contrary, L. petersonii EO 0.5 μg/mL induced a 79.88% inhibition of S. aureus biofilm, maintaining a high metabolic activity (90.89%) compared to the control. Moreover, this EO showed inhibitory activity against radical elongation of Solanum lycopersicum and the germination of radish. On the contrary, E. gunnii EO showed no phytotoxic activity., (Copyright © 2020 Caputo, Smeriglio, Trombetta, Cornara, Trevena, Valussi, Fratianni, De Feo and Nazzaro.)

Background: Anacardium occidentale L. is a tropical plant used for the treatment of inflammatory diseases. The goal of the present work was to investigate the anti-inflammatory and anti-oxidant potential of oral administration of cashew nuts (from Anacardium occidentale L.) in a mouse model of colitis., Methods: Induction of colitis was performed by intrarectally injection of dinitrobenzene sulfonic acid (DNBS). Cashew nuts were administered daily orally (100 mg/kg) in DNBS-injected mice., Results: Four days after DNBS, histological and macroscopic colon alterations as well as marked clinical signs and increased cytokine production were observed. Neutrophil infiltration, measured by myeloperoxidase (MPO) positive immunostaining, was correlated with up-regulation of adhesion molecules ICAM-1 and P-selectin in colons. Oxidative stress was detected with increased malondialdehyde (MDA) levels, nitrotyrosine, and poly ADP-ribose polymerase (PARP) positive staining in inflamed colons. Oral treatment with cashew nuts reduced histological, macroscopic damage, neutrophil infiltration, pro-inflammatory cytokines and MDA levels, as well as nitrotyrosine, PARP and ICAM-1, and P-selectin expressions. Colon inflammation could be related to nuclear factor (NF)-kB pathway activation and reduced manganese superoxide dismutase (MnSOD) antioxidant activity. Cashew nuts administration inhibited NF-kB and increased MnSOD antioxidant expressions., Conclusions: The results suggested that oral assumption of cashew nuts may be beneficial for the management of colitis.

: Citrus spp. are among the most widespread plants cultivated worldwide and every year millions of tons of fruit, juices, or processed compounds are produced and consumed, representing one of the main sources of nutrients in human diet. Among these, the flavonoids play a key role in providing a wide range of health beneficial effects. Apigenin, diosmetin, luteolin, acacetin, chrysoeriol, and their respective glycosides, that occur in concentrations up to 60 mg/L, are the most common flavones found in Citrus fruits and juices. The unique characteristics of their basic skeleton and the nature and position of the substituents have attracted and stimulated vigorous investigations as a consequence of an enormous biological potential, that manifests itself as (among other properties) antioxidant, anti-inflammatory, antiviral, antimicrobial, and anticancer activities. This review analyzes the biochemical, pharmacological, and biological properties of Citrus flavones, emphasizing their occurrence in Citrus spp. fruits and juices, on their bioavailability, and their ability to modulate signal cascades and key metabolic enzymes both in vitro and in vivo. Electronic databases including PubMed, Scopus, Web of Science, and SciFinder were used to investigate recent published articles on Citrus spp. in terms of components and bioactivity potentials., Competing Interests: The authors declare no conflict of interest.

Natural compounds are a prominent source of novel antiviral drugs. Several reports have previously shown the antimicrobial activity of pistachio polyphenol extracts. Therefore, the aim of our research was to investigate the activity of polyphenol-rich extracts of natural shelled (NPRE) pistachios kernels ( Pistacia vera L.) on herpes simplex virus type 1 (HSV-1) replication. The Vero cell line was used to assess the cytotoxicity and antiviral activity. The cell viability was calculated by detection of cellular ATP after treatment with various concentrations of NPRE. For antiviral studies, five nontoxic-concentrations (0.1, 0.2, 0.4, 0.6, 0.8 mg/mL) were tested. Our study demonstrated that treatment with NPRE (0.4, 0.6, 0.8 mg/mL) reduced the expression of the viral proteins ICP8 (infected cell polypeptide 8), UL42 (unique long UL42 DNA polymerase processivity factor) , and US11 (unique short US11 protein), and resulted in a decrease of viral DNA synthesis. The 50% cytotoxic concentration (CC 50 ), 50% inhibitory concentration (EC 50 ), and the selectivity index (SI) values for NPRE were 1.2 mg/mL, 0.4mg/mL, and 3, respectively. Furthermore, we assessed the anti-herpetic effect of a mix of pure polyphenol compounds (NS MIX) present in NPRE. In conclusion, our findings indicate that natural shelled pistachio kernels have remarkable inhibitory activity against HSV-1., Competing Interests: The authors declare no conflict of interest.

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 H 2 O 2 (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.

Due to their antimicrobial and antiviral activity potential in vitro, polyphenols are gaining a lot of attention from the pharmaceutical and healthcare industries. A novel antiviral and antimicrobial approach could be based on the use of polyphenols obtained from natural sources. Here, we tested the antibacterial and antiviral effect of a mix of polyphenols present in natural almond skin (NS MIX). The antimicrobial potential was evaluated against the standard American Type Culture Collection (ATCC) and clinical strains of Staphylococcus aureus , including methicillin-resistant (MRSA) strains, by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Herpes simplex virus type I was used for the antiviral assessment of NS MIX by plaque assay. Furthermore, we evaluated the expression of viral cascade antigens. NS MIX exhibited antimicrobial (MIC values of 0.31-1.25 mg/ml) and antiviral activity (decrease in the viral titer ** p < 0.01, and viral DNA accumulation * p < 0.05) against Staphylococcus aureus and HSV-1, respectively. Amongst the isolated compounds, the aglycones epicatechin and catechin showed the greatest activity against S. aureus ATCC 6538P (MIC values of 0.078-0.15 and 0.15 mg/ml, respectively), but were not active against all the other strains. These results could be used to develop novel products for topical use.

Background: 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., Objectives: 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., Methods: 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., Results: A rise in the thickness of the epidermis as well as an appropriate maturation and protein expression (Loricrin, Fillagrin, E-Cadherin and Cytokeratins 5&6) 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., Conclusions: 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.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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, IC 50 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 (IC 50 258.25 μg/mL). Data from MTT analysis indicate that the cytotoxicity of EO, evaluated on L929 mouse fibroblasts, is very low, with an IC 50 higher than 500 μg/mL at 48 h. Rat neuronal networks subjected to EO showed a concentration-dependent inhibition of spontaneous electrical activity. Results indicate that C. lumia EO could be an important source of natural antioxidants suggesting an important preventive role in the onset of oxidative stress-related pathologies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

This study compares in vitro and in vivo models of lipid digestion from almond particles within a complex food matrix (muffins) investigating whether the cell-wall barrier regulates the bioaccessibility of nutrients within this matrix. Muffins containing small (AF) or large (AP) particles of almond were digested in triplicate using an in vitro dynamic gastric model (DGM, 1 h) followed by a static duodenal digestion (8 h). AF muffins had 97.1 ± 1.7% of their lipid digested, whereas AP muffins had 57.6 ± 1.1% digested. In vivo digestion of these muffins by an ileostomy volunteer (0-10 h) gave similar results with 96.5% and 56.5% lipid digested, respectively. The AF muffins produced a higher postprandial triacylglycerol iAUC response (by 61%) than the AP muffins. Microstructural analysis showed that some lipid remained encapsulated within the plant tissue throughout digestion. The cell-wall barrier mechanism is the main factor in regulating lipid bioaccessibility from almond particles.

The aim of this work is to provide an update from an overview of the literature of the most frequently consumed herbal remedies during pregnancy, both alone and concomitantly with prescribed medications and particularly on their side effects to the mother and fetus. We have also analyzed some of the adverse interactions that may occur due to concomitant use of herbal and pharmaceutical products during pregnancy. Herbal remedies are not evaluated according to the same standards as pharmaceuticals, and in the USA some of it are not licensed but sold as food supplements. There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbal medicines used in pregnancy and lactation. If 'traditional use' is the only available information, the pregnant woman should be made aware of this to enable her to make an informed decision concerning potential use., (Copyright © 2014 John Wiley & Sons, Ltd.)

Bilberries are a rich dietary source of various phytonutrients, including anthocyanins which contribute greatly to their antioxidant capacity and have demonstrated a broad spectrum of biomedical functions. These include protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses and several degenerative diseases. Berry anthocyanins also improve neuronal and cognitive brain functions, ocular health as well as protecting genomic DNA integrity. In recent years, sales of many dietary supplements/pharmaceutical products containing anthocyanins in various dosages and formulations have been made by advertising their wide range of beneficial effects. However, there is a heightened risk of distributing deteriorated formulations to consumers due to lax regulations, in particular those applicable to phytochemical characterization and extract standardization, and in terms of quality regarding the stability of anthocyanins. Anthocyanin pigments readily degrade during industrial processing and this can have a dramatic impact on color quality and may also affect nutritional/pharmaceutical properties. This review aims to summarize the main health effects of bilberry extract used in several food supplements/pharmaceutical formulations focusing on some important aspects of anthocyanin degradation during processing and storage. It will also describe the main technological strategies which can give active ingredients greater stability, solubility and dispersibility in order to enhance formulation quality which is of great interest to the consumer and industry due to its direct and indirect impact on consumer health.