Effect of in vitro simulated digestion on the anti-Helicobacter Pylori activity of different Propolis extracts.

Helicobacter pylori (HP) is among the most common pathogens causing infection in humans worldwide. Oxidative stress and gastric inflammation are involved in the progression of HP-related gastric diseases, and they can be targeted by integrating conventional antibiotic treatment with polyphenol-enriched natural products. In this work, we characterised three different propolis extracts and evaluated their stability under in vitro simulated gastric digestion, compared to their main constituents alone. The extract with the highest stability to digestion (namely, the dark propolis extract, DPE) showed a minimum bactericidal concentration (MBC) lower than 1 mg/mL on HP strains with different virulence factors. Finally, since urease is one of the virulence factors contributing to the establishment of a microenvironment that promotes HP infection, we evaluated the possible inhibition of this enzyme by using molecular docking simulations and in vitro colorimetric assay, showing that galangin and pinocembrin may be involved in this activity.

Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling.

Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD- and terpenes-enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV-2 microglial cells, compared with CBD and ß-caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS-induced upregulation of the pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α was significantly attenuated by CSE and only partially by CBD, whereas CAR was ineffective. In BV-2 cells, these anti-inflammatory effects exerted by CSE phytocomplex were only partially dependent on CB2r modulation and they were mediated by the regulation of enzymes responsible for the endocannabinoids metabolism, by the inhibition of reactive oxygen species release and the modulation of JNK/p38 cascade with consequent NF-κB p65 nuclear translocation suppression. Our data suggest that C. sativa phytocomplex and its multitarget mechanism could represent a novel therapeutic strategy for neuroinflammatory-related diseases.

Achillea moschata Wulfen: From Ethnobotany to Phytochemistry, Morphology, and Biological Activity.

A multidisciplinary investigation on Achillea moschata Wulfen (Asteraceae) is outlined herein. This work, part of the European Interreg Italy-Switzerland B-ICE project, originated from an ethnobotanical survey performed in Chiesa in Valmalenco (Sondrio, Lombardy, Northern Italy) in 2019-2021 which highlighted this species' relevance of use in folk medicine to treat gastrointestinal diseases. In addition, this contribution included analyses of the: (a) phytochemical profile of the aqueous and methanolic extracts of the dried flower heads using LC-MS/MS; (b) morpho-anatomy and histochemistry of the vegetative and reproductive organs through Light, Fluorescence, and Scanning Electron Microscopy; (c) biological activity of the aqueous extract concerning the antioxidant and anti-inflammatory potential through cell-based in vitro models. A total of 31 compounds (5 phenolic acids, 13 flavonols, and 13 flavones) were detected, 28 of which included in both extracts. Covering and secreting trichomes were observed: the biseriate 10-celled glandular trichomes prevailing on the inflorescences represented the main sites of synthesis of the polyphenols and flavonoids detected in the extracts, along with volatile terpenoids. Finally, significant antioxidant and anti-inflammatory activities of the aqueous extract were documented, even at very low concentrations; for the first time, the in vitro tests allowed us to formulate hypotheses about the mechanism of action. This work brings an element of novelty due to the faithful reproduction of the traditional aqueous preparation and the combination of phytochemical and micromorphological research approaches.

Phytotherapy in the Management of Diabetes: A Review.

Phytotherapy has long been a source of medicinal products and over the years there have been many attempts to use herbal medicines for the treatment of diabetes. Several medicinal plants and their preparations have been demonstrated to act at key points of glucidic metabolism. The most common mechanisms of action found include the inhibition of α-glucosidase and of AGE formation, the increase of GLUT-4 and PPARs expression and antioxidant activity. Despite the large amount of literature available, the actual clinical effectiveness of medicinal plants in controlling diabetes-related symptoms remains controversial and there is a crucial need for stronger evidence-based data. In this review, an overview of the medicinal plants, which use in the management of diabetes is supported by authoritative monographs, is provided. References to some species which are currently under increasing clinical investigation are also reported.

Comparative effects of a fixed Polypodium leucotomos/Pomegranate combination versus Polypodium leucotomos alone on skin biophysical parameters.

OBJECTIVES: Polypodium leucotomos extract is a commonly used systemic photoprotective agent. In an exploratory fashion, the current study aimed to compare the effects of oral supplementation with a fixed Polypodium leucotomos/pomegranate combination (PPmix®) versus Polypodium leucotomos alone (Fernblock®) on skin biophysical parameters of Caucasian adults. METHODS: Forty healthy adult volunteers (20 males and 20 females; mean age: 37.2±5.5 years) were randomized in a 1:1 fashion to a fixed Polypodium leucotomos/pomegranate combination (480 mg/day; n=20) or Polypodium leucotomos alone (480 mg/day; n=20) for 3 months. Six skin biophysical parameters (skin sebum content, hydration, transepidermal water loss [TEWL], erythema index, melanin index, and elasticity) were measured at baseline and after 3 months by personnel blinded to participant allocation. RESULTS: At the end of the study, hydration and elasticity were significantly improved and TEWL was reduced in both groups, without significant intergroup differences. The erythema index was decreased by both treatments, although the fixed Polypodium leucotomos/pomegranate combination was significantly more effective. Finally, melanin index and skin sebum content were reduced by the fixed Polypodium leucotomos/pomegranate combination, whereas Polypodium leucotomos alone did not affect them. CONCLUSIONS: Our results suggest that a fixed Polypodium leucotomos/pomegranate combination provides a greater improvement of skin biophysical parameters compared to Polypodium leucotomos alone in adult Caucasians. Our findings may have implications for optimizing systemic skin photoprotection and beautification strategies.

Consensus screening for a challenging target: the quest for P-glycoprotein inhibitors.

ATP-binding cassette (ABC) transporters are a large family of proteins involved in membrane transport of a wide variety of substrates. Among them, ABCB1, also known as MDR-1 or P-glycoprotein (P-gp), is the most characterized. By exporting xenobiotics out of the cell, P-gp activity can affect the ADME properties of several drugs. Moreover, P-gp has been found to mediate multidrug resistance in cancer cells. Thus, the inhibition of P-gp activity may lead to increased absorption and/or intracellular accumulation of co-administered drugs, enhancing their effectiveness. Using the human-mouse chimeric cryoEM 3D structure of the P-gp in the inhibitor-bound intermediate form (PDBID: 6qee), approximately 200 000 commercially available natural compounds from the ZINC database were virtually screened. To build a model able to discriminate between substrate and inhibitors, two datasets of compounds with known activity, including P-gp inhibitors, substrates, and inactive molecules were also docked. The best docking pose of selected substrates and inhibitors were used to generate 3D common feature pharmacophoric models that were combined with the Autodock Vina binding energy values to prioritize compounds for visual inspection. With this consensus approach, 13 potential candidates were identified and then tested for their ability to inhibit P-gp, using zosuquidar, a third generation P-gp inhibitor, as a reference drug. Eight compounds were found to be active with 6 of them having an IC50 lower than 5 µM in a membrane-based ATPase activity assay. Moreover, the P-gp inhibitory activity was also confirmed by two different cell-based in vitro methods. Both retrospective and prospective results demonstrate the ability of the combined structure-based pharmacophore modeling and docking-based virtual screening approach to predict novel hit compounds with inhibitory activity toward P-gp. The resulting chemical scaffolds could serve as inspiration for the optimization of novel and more potent P-gp inhibitors.

Investigation on the Efficacy of Two Food Supplements Containing a Fixed Combination of Selected Probiotics and ß-Glucans or Elderberry Extract for the Immune System: Modulation on Cytokines Expression in Human THP-1 and PBMC.

Several herbal and other natural products are used as ingredients in food supplements to strengthen immunity even if, very often, marketed products are proposed without a clear rationale or experimental evidence. In this study, we aimed to investigate the effect on human monocytes (THP-1) and on ex vivo human peripheral blood mononuclear cells (PBMC) of two formulations, one containing Bifidobacterium animalis subsp. lactis Bl-04® with ß-glucans (for adults) and one containing Lactobacillus rhamnosus CRL1505 with elderberry extract (for children). We compared formulations with single ingredients, with bacterial lipopolysaccharide (LPS) and the drug pidotimod; cytokines expression level was evaluated testing different concentrations of samples at two exposure times. As expected, LPS caused a non-specific huge upregulation of cytokines expression both in THP-1 and in PBMC, whereas pidotimod mainly upregulated IL-2 in PBMC and IL-8 in THP-1. The two formulations showed a difference between a pro-inflammatory stimulus such as LPS, and also from an immunostimulant drug, such as pidotimod, as they mainly upregulated the expression of IL-6 and IL-10 in PBMC but not in THP-1, in a concentration-dependent mode. Probiotics were shown to play a major role, but ß-glucans and elderberry extract exerted a synergistic activity. This work demonstrated that combining selected probiotics with other natural products having immunomodulatory properties is an interesting strategy to develop innovative formulations in the sector of food supplements.

Extraction, purification and in vitro assessment of the antioxidant and anti-inflammatory activity of policosanols from non-psychoactive Cannabis sativa L.

Policosanols (PCs) are bioactive compounds extracted from different natural waxes. In this work, the purification, characterization and assessment of the antioxidant and anti-inflammatory activity was carried out on PCs from an innovative source, i.e. a waxy material from supercritical-fluid extraction (SFE) of non-psychoactive Cannabis sativa L. (hemp) inflorescences. Starting from this material, PCs were obtained by microwave-assisted trans-esterification and hydrolysis, followed by preparative liquid chromatography under normal phase conditions. The purified product was characterized using high-performance liquid chromatography (HPLC) with an evaporative light scattering detector (ELSD). In vitro cell-free and cell-based antioxidant and anti-inflammatory assays were then performed to assess their bioactivity. HPLC-ELSED analysis of the purified mixture from hemp wax revealed C26OH and C28OH as the main compounds. In vitro assays indicated an inhibition of intracellular reactive oxygen species (ROS) production, a reduction of nuclear factor kappa B (NF-κB) activation and of the activity of the neutrophil elastase. Immunoblotting assays allowed us to hypothesize the mechanism of action of the compounds of interest, given the higher levels of MAPK-activated protein kinase 2 (MK2) and heme oxygenase-1 (HO-1) protein expression in the PC pretreated HaCaT cells. In conclusion, even if more research is needed to unveil other molecular mechanisms involved in hemp PC activity, the results of this work suggest that these compounds may have potential for use in oxinflammation processes.

In vitro Digestion of Phaseolus vulgaris L. Cooked Beans Induces Autophagy in Colon Cancer Cells.

Phaseolus vulgaris L. (common bean) contains high levels of proteins, unsaturated fatty acids, minerals, fibers, and vitamins, and for this reason, it represents an essential component of the diet. More than 40,000 varieties of beans have been recognized and are staple foods in the traditional cuisine of many countries. In addition to its high nutritional value, P. vulgaris is also characterized by its nutraceutical properties and favors environmental sustainability. In this manuscript, we studied two different varieties of P. vulgaris, Cannellino and Piattellino. We investigated the effects of traditional processing (soaking and cooking) and in vitro gastrointestinal digestion of beans on their phytochemical composition and anticancer activity. Using HT29 and HCT116 colon cancer cell lines, we showed that the extract obtained after gastrointestinal digestion of cooked beans (the bioaccessible fraction, BF) induces cell death through the induction of the autophagic process. We demonstrated that the BF of Cannellino and Piattellino beans at the concentration of 100 µg/mL reduces cell vitality, measured by MMT assay, of both HT29 (88.41% ± 5.79 and 94.38% ± 0.47) and HCT116 (86.29% ± 4.3 and 91.23% ± 0.52) cell lines. Consistently, the treatment of HT29 cells with 100 µg/mL of Cannellino and Piattellino BFs reduced clonogenicity by 95% ± 2.14 and 96% ± 0.49, respectively. Moreover, the activity of extracts appeared to be selective for colon cancer cells. The data shown in this work further confirm P. vulgaris to be among foods with beneficial effects for human health.

Medical Ethnobotany of the Bissau-Guinean Community of Migrants Living in Northern Italy and Comparison with the Ethnopharmacology of Guinea-Bissau.

This study compares the knowledge of medicinal plants of Bissau-Guinean migrants now established in Italy with the ethnopharmacology still present in their country of origin. We also investigated how traditional ethnobotanical knowledge is changing following the phenomenon of migration from Africa to Europe. The ethnobotanical data were collected during 2017-2018, by interviewing 49 informants belonging to 8 ethnic groups, living in 8 provinces of northern Italy. The final inventory of botanical taxa included 81 species belonging to 34 families, with Fabaceae and Malvaceae the most represented, followed by Euphorbiaceae, Apocynaceae, Combretaceae, and Solanaceae. Plant remedies were used to treat 21 ailment categories, such as fever, internal infections, intestinal and respiratory problems, and pains. The traditional ethnobotanical knowledge of Bissau-Guinean migrants in Italy was associated with gender, with women showing the highest knowledge. In addition, a negative relationship was observed between the maintenance of this knowledge and the number of years migrants have spent in Italy. Overall, a loss of knowledge was observed in the less numerous ethnic groups. However, traditional preparations based on plants from the country of origin are in general well preserved to maintain a good state of health. Our work could help in transferring to the next generation the cultural heritage of Bissau-Guinean people permanently moved to European Countries.

A Novel Perilla frutescens (L.) Britton Cell-Derived Phytocomplex Regulates Keratinocytes Inflammatory Cascade and Barrier Function and Preserves Vaginal Mucosal Integrity In Vivo.

In the last years, the medicinal plant Perilla frutescens (L.) Britton has gained scientific interest because leaf extracts, due to the presence of rosmarinic acid and other polyphenols, have shown anti-allergic and skin protective potential in pre-clinical studies. Nevertheless, the lack of standardized extracts has limited clinical applications to date. In this work, for the first time, a standardized phytocomplex of P. frutescens, enriched in rosmarinic acid and total polyphenols, was produced through innovative in vitro cell culture biotechnology and tested. The activity of perilla was evaluated in an in vitro inflammatory model of human keratinocytes (HaCaT) by monitoring tight junctions, filaggrin, and loricrin protein levels, the release of pro-inflammatory cytokines and JNK MAPK signaling. In a practical health care application, the perilla biotechnological phytocomplex was tested in a multilayer model of vaginal mucosa, and then, in a preliminary clinical observation to explore its capacity to preserve vaginal mucosal integrity in women in peri-menopause. In keratinocytes cells, perilla phytocomplex demonstrated to exert a marked activity in epidermis barrier maintenance and anti-inflammatory effects, preserving tight junction expression and downregulating cytokines release through targeting JNK activation. Furthermore, perilla showed positive effects in retaining vaginal mucosal integrity in the reconstructed vaginal mucosa model and in vivo tests. Overall, our data suggest that the biotechnological P. frutescens phytocomplex could represent an innovative ingredient for dermatological applications.

An open-label study on the short-term effects of a novel EFSA-compliant nutraceutical combination in mild-to-moderate hypercholesterolemia.

Objective: Recently, the European Food Safety Authority (EFSA) has recommended to limit the use of total monacolins in red yeast rice (RYR) products to a dose <3 mg/day. However, data concerning the lipid lowering efficacy of the reduced dosage remain limited. A monacolin dose reduced due to safety issues may be expected to be less effective as a lipid lowering strategy and, for this reason, nutraceutical combinations with other active compounds may offer a viable solution as they can act synergistically through different mechanisms. Materials and Methods: This 8-week open-label study was designed to investigate the safety and efficacy of a novel ESFA-compliant lipid lowering nutraceutical combination (Colestarmony Plus®; containing total monacolins from RYR at a dose of 2.9 mg/day, a highly bioavailable berberine formulation, and pomegranate extract) in subjects (n=40) with mild-to-moderate hypercholesterolemia and no history of cardiovascular disease. Results: After 8 weeks of supplementation, Colestarmony Plus® significantly reduced total cholesterol (-10.4%, p<0.05), low-density lipoprotein cholesterol (-14.8%, p<0.05), oxidized low-density lipoprotein cholesterol (-12.0%, p<0.05), and high-sensitivity C-reactive protein (-14.0%, p<0.05) compared with baseline values. A subgroup of 22 patients underwent measurements of flow-mediated dilation, with values increasing by 18.0% at 8 weeks with respect to baseline (p<0.05). The supplement was generally well-tolerated. Conclusion: Our short-term results indicate that the tested ESFA-compliant nutraceutical is effective in a primary prevention setting, even by providing only <3 mg/day of monacolins.

Investigation on the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract in an in vitro model of excitotoxicity.

The purpose of this study was to evaluate the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract (CSE) and its main constituents, cannabidiol and ß-caryophyllene. An in vitro model of glutamate-induced neuronal excitotoxicity using SH-SY5Y cells was optimized. The impact of CSE on glutamate-impaired cell viability, brain-derived neurotrophic factor release, CB1 protein expression, and ERK levels was evaluated. The involvement of CB1 modulation was verified by the cotreatment with the CB1 antagonist AM4113. CSE was able to significantly protect SH-SY5Y from glutamate-impaired cell viability, and to counteract the changes in brain-derived neurotrophic factor levels, with a mechanism of action involving ERK modulation. Moreover, CSE completely reversed the reduction of CB1 receptor expression induced by glutamate, and the presence of the CB1 antagonist AM4113 reduced CSE effectiveness, suggesting that CBr play a role in the modulation of neuronal excitotoxicity. This work demonstrated the in vitro effectiveness of CSE as a neuroprotective agent, proposing the whole cannabis phytocomplex as a more effective strategy, compared to its main constituents alone, and suggested further investigations by using more complex cell models before moving to in vivo studies.

Anti-inflammatory activity of a fixed combination of probiotics and herbal extract in an in-vitro model of intestinal inflammation by stimulating Caco-2 cells with LPS-conditioned THP-1 cells medium.

BACKGROUND: Inflammatory bowel disease (IBD) is an inflammatory condition of the gastrointestinal tract, characterized by chronic and relapsing immune system activation, often diagnosed in adolescence, with a rising incidence in pediatric populations. IBD results from altered interactions between gut microbes and the intestinal immune system which induce an aberrant immune response, thus anti-inflammatory or immunosuppressive therapies are generally used. Recent interest has been given to the identification of integrative and complementary approaches that could be able to restore and preserve the intestinal barrier function. METHODS: In this work, we tested the effect of a fixed combination of probiotics and herbal extract (Colikind Gocce® [CKG], Schwabe Pharma, Egna-Neumarkt, Bolzano, Italy) in an in-vitro model of intestinal inflammation. Caco-2 cells stimulated with LPS-conditioned monocytes culture medium was used as a paradigm of intestinal inflammation. The possible effect of CKG in maintaining the homeostasis of the intestinal epithelial barrier was investigated by measurement of the trans-epithelial electrical resistance, the paracellular permeability, and the release of inflammatory cytokines (TNF-α, IL-8, and IL-10). RESULTS: Results obtained in this work demonstrated that CKG is able to prevent the impairment of intestinal barrier function induced by inflammation, ameliorating the transepithelial electrical resistance and the paracellular permeability of the Caco-2 monolayer; moreover, CKG is able to counteract the increased release of TNF-a and IL-8 induced by inflammatory stimulus, thus reducing the intestinal inflammation. CONCLUSIONS: This work underlines the protective effect of CKG on intestinal barrier, reducing the damages induced by inflammatory stimulus. This suggests CKG as an interesting product in the management of intestinal inflammatory conditions.

In vitro Evaluation of Antiviral Efficacy of a Standardized Hydroalcoholic Extract of Poplar Type Propolis Against SARS-CoV-2.

Except for specific vaccines and monoclonal antibodies, effective prophylactic or post-exposure therapeutic treatments are currently limited for COVID-19. Propolis, a honeybee's product, has been suggested as a potential candidate for treatment of COVID-19 for its immunomodulatory properties and for its powerful activity against various types of viruses, including common coronaviruses. However, direct evidence regarding the antiviral activities of this product still remains poorly documented. VERO E6 and CALU3 cell lines were infected with SARS-CoV-2 and cultured in the presence of 12.5 or 25 µg/ml of a standardized Hydroalcoholic Extract acronym (sHEP) of Eurasian poplar type propolis and analyzed for viral RNA transcription, for cell damage by optical and electron microscopy, and for virus infectivity by viral titration at 2, 24, 48, and 72 h post-infection. The three main components of sHEP, caffeic acid phenethyl ester, galangin, and pinocembrin, were tested for the antiviral power, either alone or in combination. On both cell lines, sHEP showed significant effects mainly on CALU3 up to 48 h, i.e., some protection from cytopathic effects and consistent reduction of infected cell number, fewer viral particles inside cellular vesicles, reduction of viral titration in supernatants, dramatic drop of N gene negative sense RNA synthesis, and lower concentration of E gene RNA in cell extracts. Interestingly, pre-treatment of cells with sHEP before virus inoculation induced these same effects described previously and was not able to block virus entry. When used in combination, the three main constituents of sHEP showed antiviral activity at the same levels of sHEP. sHEP has a remarkable ability to hinder the replication of SARS-CoV-2, to limit new cycles of infection, and to protect host cells against the cytopathic effect, albeit with rather variable results. However, sHEP do not block the virus entry into the cells. The antiviral activity observed with the three main components of sHEP used in combination highlights that the mechanism underlying the antiviral activity of sHEP is probably the result of a synergistic effect. These data add further emphasis on the possible therapeutic role of this special honeybee's product as an adjuvant to official treatments of COVID-19 patients for its direct antiviral activity.

Chemical Profile, Antioxidant, Anti-Proliferative, Anticoagulant and Mutagenic Effects of a Hydroalcoholic Extract of Tuscan Rosmarinus officinalis.

This study aimed to characterize the chemical profile of an ethanolic extract of Tuscan Rosmarinus officinalis (Roex) and to determine its in vitro bioactivity. The content of phenolic and flavonoid compounds, hydroxycinnamic acids and triterpenoids was determined, and high-performance liquid chromatography-diode array detection (HPLC-DAD) analysis revealed that rosmarinic acid and other hydroxycinnamic derivatives were the main constituents of the extract. Roex demonstrated to have both antioxidant activity and the capability to scavenge hydrogen peroxide in a concentration dependent manner. Moreover, NIH3T3 mouse fibroblasts and human breast adenocarcinoma cells MDA-MB-231 viability was influenced by the extract with an IC50 of 2.4 × 10-1 mg/mL and 4.8 × 10-1 mg/mL, respectively. The addition of Roex to the culture medium of both the above cell lines, resulted also in the reduction of cell death after H2O2 pre-treatment. The Ames test demonstrated that Roex was not genotoxic towards both TA98 and TA100 strains, with and without S9 metabolic activation. The extract, by inactivating thrombin, showed to also have an anti-coagulating effect at low concentration values. All these biological activities exerted by Roex are tightly correlated to its phytochemical profile, rich in bioactive compounds.

Nutraceuticals and Herbal Food Supplements for Weight Loss: Is There a Prebiotic Role in the Mechanism of Action?

Numerous nutraceuticals and botanical food supplements are used with the intention of modulating body weight. A recent review examined the main food supplements used in weight loss, dividing them according to the main effects for which they were investigated. The direct or indirect effects exerted on the intestinal microbiota can also contribute to the effectiveness of these substances. The aim of this review is to evaluate whether any prebiotic effects, which could help to explain their efficacy or ineffectiveness, are documented in the recent literature for the main nutraceuticals and herbal food supplements used for weight loss management. Several prebiotic effects have been reported for various nutraceutical substances, which have shown activity on Bifidobacterium spp., Lactobacillus spp., Akkermansia muciniphila, Faecalibacterium prausnitzi, Roseburia spp., and the Firmicutes/Bacteroidetes ratio. Different prebiotics have beneficial effects on weight and the related metabolic profile, in some cases even acting on the microbiota with mechanisms that are completely independent from those nutraceuticals for which certain products are normally used. Further studies are necessary to clarify the different levels at which a nutraceutical substance can exert its action.

Polyphenols: From Theory to Practice.

BACKGROUND: The importance of polyphenols in human health is well known; these compounds are common in foods, such as fruits, vegetables, spices, extra virgin olive oil and wine. On the other hand, the different factors that modulate the biological activity of these compounds are less well known. Conceptualization of the work: In this review we took into account about 200 relevant and recent papers on the following topics: "polyphenols bioavailability", "polyphenols matrix effect", "food matrix effect", "polyphenols-cytochromes interaction", after having reviewed and updated information on chemical classification and main biological properties of polyphenols, such as the antioxidant, anti-radical and anti-inflammatory activity, together with the tricky link between in vitro tests and clinical trials. KEY FINDINGS: the issue of polyphenols bioavailability and matrix effect should be better taken into account when health claims are referred to polyphenols, thus considering the matrix effect, enzymatic interactions, reactions with other foods or genetic or gender characteristics that could interfere. We also discovered that in vitro studies often underrate the role of phytocomplexes and thus we provided practical hints to describe a clearer way to approach an investigation on polyphenols for a more resounding transfer to their use in medicine.

A honokiol-enriched Magnolia officinalis Rehder & E.H. Wilson. bark extract possesses anxiolytic-like activity with neuroprotective effect through the modulation of CB1 receptor.

OBJECTIVES: The exposure of neurons to an excessive excitatory stimulation induces the alteration of the normal neuronal function. Mood disorders are among the first signs of alterations in the central nervous system function. Magnolia officinalis bark extract has been extensively used in the traditional medicine systems of several countries, showing several pharmacological activities. Honokiol, the main constituent of M. officinalis, is a GABA modulator and a CB1 agonist, which is deeply investigated for its role in modulating mood disorders. METHODS: Thus, we evaluated the possible neuroprotective effect of a standardized M. officinalis bark extract (MOE), enriched in honokiol, and its effect on animal mood behavioural tests and in an in vitro model of excitotoxicity. KEY FINDINGS: MOE showed neuroprotective effect using SH-SY5Y cells, by normalizing brain-derived neurotrophic factor release. Then, we tested the effect of MOE in different behavioural tests evaluating anxiety and depression and we observed a selective anxiolytic-like effect. Finally, we confirmed the involvement of CB1 in the final effect of MOE by the co-administration of the CB1 antagonist, AM251. CONCLUSION: These results suggest that MOE could be considered an effective and safe anxiolytic candidate with neuroprotective activity.

Cannabidiol Isolated From Cannabis sativa L. Protects Intestinal Barrier From In Vitro Inflammation and Oxidative Stress.

The relevance and incidence of intestinal bowel diseases (IBD) have been increasing over the last 50 years and the current therapies are characterized by severe side effects, making essential the development of new strategies that combine efficacy and safety in the management of human IBD. Herbal products are highly considered in research aimed at discovering new approaches for IBD therapy and, among others, Cannabis sativa L. has been traditionally used for centuries as an analgesic and anti-inflammatory remedy also in different gastrointestinal disorders. This study aims to investigate the effects of different C. sativa isolated compounds in an in vitro model of intestinal epithelium. The ability of treatments to modulate markers of intestinal dysfunctions was tested on Caco-2 intestinal cell monolayers. Our results, obtained by evaluation of ROS production, TEER and paracellular permeability measurements and tight junctions evaluation show Cannabidiol as the most promising compound against intestinal inflammatory condition. Cannabidiol is able to inhibit ROS production and restore epithelial permeability during inflammatory and oxidative stress conditions, suggesting its possible application as adjuvant in IBD management.