Redox State Modulatory Activity and Cytotoxicity of Olea europaea L. (Oleaceae) Leaves Extract Enriched in Polyphenols Using Macroporous Resin.

The food products derived from Olea europaea are a fundamental part of the Mediterranean diet, and their health-promoting effects are well known. In this study, we analyzed the phytochemical characteristics, the redox state modulatory activity, and the cytotoxic effect of an olive leaf aqueous extract enriched by macroporous resin on different tumor and normal cell lines (LNCaP, PC3, HFF-1). HPLC-DAD analysis, the Folin-Ciocalteu and aluminum chloride methods confirmed the qualitatively and quantitatively high content of phenolic compounds (130.02 ± 2.3 mg GAE/g extract), and a DPPH assay (IC50 = 100.00 ± 1.8 µg/mL), the related antioxidant activity. The biological investigation showed a significant cytotoxic effect, highlighted by an MTT test and the evident cellular morphological changes, on two prostate cancer cell lines. Remarkably, the extract was practically non-toxic on HFF-1 at the concentrations (100, 150, 300 µg/mL) and exposure times tested. Hence, the results are selective for tumor cells. The underlying cytotoxicity was associated with the decrease in ROS production (55% PC3, 42% LNCaP) and the increase in RSH levels (>50% PC3) and an LDH release assay (50% PC3, 40% LNCaP, established necrosis as the main cell death mechanism.

Natural Compounds and Glutathione: Beyond Mere Antioxidants.

The tripeptide glutathione plays important roles in many cell processes, including differentiation, proliferation, and apoptosis; in fact, disorders in glutathione homeostasis are involved both in the etiology and in the progression of several human diseases, including cancer. Natural compounds have been found to modulate glutathione levels and function beyond their role as mere antioxidants. For example, certain compounds can upregulate the expression of glutathione-related enzymes, increase the availability of cysteine, the limiting amino acid for glutathione synthesis, or directly interact with glutathione and modulate its function. These compounds may have therapeutic potential in a variety of disease states where glutathione dysregulation is a contributing factor. On the other hand, flavonoids' potential to deplete glutathione levels could be significant for cancer treatment. Overall, while natural compounds may have potential therapeutic and/or preventive properties and may be able to increase glutathione levels, more research is needed to fully understand their mechanisms of action and their potential benefits for the prevention and treatment of several diseases. In this review, particular emphasis will be placed on phytochemical compounds belonging to the class of polyphenols, terpenoids, and glucosinolates that have an impact on glutathione-related processes, both in physiological and pathological conditions. These classes of secondary metabolites represent the most food-derived bioactive compounds that have been intensively explored and studied in the last few decades.

Wild Artichoke (Cynara cardunculus subsp. sylvestris, Asteraceae) Leaf Extract: Phenolic Profile and Oxidative Stress Inhibitory Effects on HepG2 Cells.

Cynara cardunculus subsp. sylvestris (wild artichoke) is widespread in Sicily, where it has been used for food and medicinal purposes since ancient times; decoctions of the aerial parts of this plant have been traditionally employed as a remedy for different hepatic diseases. In this study, the phenolic profile and cell-free antioxidant properties of the leaf aqueous extract of wild artichokes grown in Sicily (Italy) were investigated. The crude extract was also tested in cells for its antioxidant characteristics and potential oxidative stress inhibitory effects. To resemble the features of the early stage of mild steatosis in humans, human HepG2 cells treated with free fatty acids at the concentration of 1.5 mM were used. HPLC-DAD analysis revealed the presence of several phenolic acids (caffeoylquinic acids) and flavonoids (luteolin and apigenin derivatives). At the same time, DPPH assay showed a promising antioxidant power (IC50 = 20.04 ± 2.52 µg/mL). Biological investigations showed the safety of the crude extract and its capacity to counteract the injury induced by FFA exposure by restoring cell viability and counteracting oxidative stress through inhibiting reactive oxygen species and lipid peroxidation and increasing thiol-group levels. In addition, the extract increased mRNA expression of some proteins implicated in the antioxidant defense (Nrf2, Gpx, and SOD1) and decreased mRNA levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß), which were modified by FFA treatment. Results suggest that the total phytocomplex contained in wild artichoke leaves effectively modulates FFA-induced hepatic oxidative stress.

Chemical Profile, Antioxidant and Cytotoxic Activity of a Phenolic-Rich Fraction from the Leaves of Brassica fruticulosa subsp. fruticulosa (Brassicaceae) Growing Wild in Sicily (Italy).

Recently, our research team has started a study on Brassica fruticulosa subsp. fruticulosa, an edible plant traditionally used to treat various ailments, little investigated to date. Good in vitro antioxidant properties were highlighted for the leaf hydroalcoholic extract, with the secondary higher than the primary ones. In continuation of the ongoing research, this work was designed to elucidate the antioxidant properties of the phenolic compounds contained in the extract. For this purpose, a phenolic-rich ethyl acetate fraction (Bff-EAF) was obtained from the crude extract by liquid-liquid extraction. The phenolic composition was characterized by HPLC-PDA/ESI-MS analysis and the antioxidant potential was investigated by different in vitro methods. Furthermore, the cytotoxic properties were evaluated by MTT, LDH and ROS determinations on human colorectal epithelial adenocarcinoma cells (CaCo-2) and human normal fibroblasts (HFF-1). Twenty phenolic compounds (flavonoid and phenolic acid derivatives) were identified in Bff-EAF. The fraction exhibited good radical scavenging activity in the DPPH test (IC50 = 0.81 ± 0.02 mg/mL), and moderate reducing power (ASE/mL = 13.10 ± 0.94) and chelating properties (IC50 = 2.27 ± 0.18 mg/mL), contrary to what previously observed for the crude extract. Bff-EAF reduced in a dose-dependent manner CaCo-2 cell proliferation after 72 h of treatment. This effect was accompanied by the destabilization of the cellular redox state due to the antioxidant and pro-oxidant activities displayed by the fraction at lower and higher concentrations. No cytotoxic effect was observed on HFF-1 fibroblasts, used as control cell line.

Chemical, Antioxidant and Biological Studies of Brassica incana subsp. raimondoi (Brassicaceae) Leaf Extract.

Brassica incana subsp. raimondoi is an endemic taxon present in a restricted area located on steep limestone cliffs at an altitude of about 500 m a.s.l. in eastern Sicily. In this research, for the first time, studies on the phytochemical profile, the antioxidant properties in cell-free and cell-based systems, the cytotoxicity on normal and cancer cells by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, and on Artemia salina Leach, were performed. The total phenolic, flavonoid, and condensed tannin contents of the leaf hydroalcoholic extract were spectrophotometrically determined. Ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) analysis highlighted the presence of several phenolic acids, flavonoids, and carotenoids, while High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) identified various kaempferol and isorhamnetin derivatives. The extract exhibited different antioxidant properties according to the five in vitro methods used. Cytotoxicity by MTT assay evidenced no impact on normal human fibroblasts (HFF-1) and prostate cancer cells (DU145), and cytotoxicity accompanied by necrotic cell death for colon cancer cells (CaCo-2) and hepatoma cells (HepG2), starting from 100 µg/mL and 500 µg/mL, respectively. No cytotoxic effects were detected by the A. salina lethality bioassay. In the H2O2-induced oxidative stress cell model, the extract counteracted cellular reactive oxygen species (ROS) production and preserved non-protein thiol groups (RSH) affected by H2O2 exposure in HepG2 cells. Results suggest the potential of B. incana subsp. raimondoi as a source of bioactive molecules.

Biological Investigation and Chemical Study of Brassica villosa subsp. drepanensis (Brassicaeae) Leaves.

Brassica villosa subsp. drepanensis (Caruel) Raimondo & Mazzola, belonging to the Brassica oleracea complex, is a wild edible plant endemic to western Sicily and a relative of modern cultivated Brassica crops. In this study, the antioxidant properties, anti-inflammatory activities, enzymatic inhibition, and cytotoxicity in cancer cells of B. villosa subsp. drepanensis leaf ethanolic extract were analysed for the first time. In addition, its chemical profile was investigated partitioning the total 70% ethanol extract among ethyl acetate, n-butanol, and water to obtain three residues that were subjected to chromatographic separation. Two flavonol glycosides, a phenol glucoside, two amino acids, and purine/pyrimidine bases were obtained. The presence of the glucosinolate glucoiberin was detected in the water extract by UHPLC-MS analysis. The total polyphenol and flavonoid content of the 70% ethanol extract showed good antioxidant capacities and anti-inflammatory properties by reducing nitric oxide release and reactive oxygen species levels and increasing glutathione in lipopolysaccharide-stimulated RAW 264.7 cells. The extract inhibited the enzymatic activity of α-amylase, α-glucosidase, and, significantly, of lipase. The MTT assay showed that the extract did not affect the viability of normal HFF-1 and RAW 264.7 cells. Among the cancer cell lines tested, an antiproliferative action was only observed in CaCo-2. The cytotoxicity of the extract was further confirmed by LDH release assay and by the destabilization of the oxidative balance. Results confirmed the antioxidant properties of the crude extract responsible for the anti-inflammatory effect on healthy cells and cytotoxicity in cancer cells.

Antioxidant Efficacy of a Standardized Red Orange (Citrus sinensis (L.) Osbeck) Extract in Elderly Subjects: A Randomized, Double Blind, Controlled Study.

The world population is rapidly aging. This should cause us to reflect on the need to develop a new nutritional approach to mitigate the accumulation of reactive oxygen species (ROS)-induced damage. A randomized, double blind, controlled study was carried out on 60 elderly male and female subjects. Product efficacy was measured before and after 2 and 8 weeks of product intake. The reduced (GSH) and oxidized (GSSG) glutathione concentrations in the erythrocytes and the reactive oxygen metabolites (d-ROMs) hematic concentration were measured to assess the antioxidant efficacy. The tumor necrosis factor-alpha (TNF-α) levels in the serum were measured to assess the anti-inflammatory effectiveness. The wellbeing was assessed by Short Form Health Survey (SF-36) questionnaire (male) and by Menopause Rating Scale (MRS) (female). Blood, urine analysis and electrocardiography (ECG) were carried out to assess the product's safety. The results showed that GSH/GSSG ratio increased by 22.4% and 89.0% after 2 and 8 weeks of product intake. Serum TNF-α levels decreased by 2.5% after 8 weeks of product intake. The SF-36 QoL and the MRS questionnaire outputs indicate, preliminarily, a positive effect of the extract intake in ameliorating the wellbeing of both male and female subjects. The product was well-tolerated. Our findings suggest that the test product has antioxidant and anti-inflammatory efficacy and has a positive effect on the wellbeing of elderly female and male subjects.

Vitamin E and Non-Communicable Diseases: A Review.

Vitamin E, a nutrient found in several foods, comprises eight lipophilic vitamers, the α-, ß-, γ- and δ-tocopherols and the α-, ß-, γ- and δ-tocotrienols. This vitamin is capable of exerting antioxidant and anti-inflammatory activities, and acting as immunomodulators. Despite these well-known biological activities, the findings regarding the ability of vitamin E and its serum metabolites to prevent and/or control chronic disease are often conflicting and inconsistent. In this review, we have described the metabolism of vitamin E and its interaction with the gut microbiota, considering that these factors may be partially responsible for the divergent results obtained. In addition, we focused on the correlations between vitamin E serum levels, dietary intake and/or supplementation, and the main non-communicable diseases, including diabetes mellitus, asthma, cardiovascular diseases, and the four most common cancers (breast cancer, lung cancer, colorectal cancer, and prostate cancer) with the intention of providing an overview of its health effects in the non-communicable-diseases prevention.

Photoprotective and Antiaging Effects of a Standardized Red Orange (Citrus sinensis (L.) Osbeck) Extract in Asian and Caucasian Subjects: A Randomized, Double-Blind, Controlled Study.

The increase in solar ultraviolet radiation (UVR) that reaches the Earth's surface should make us reflect on the need to develop new approaches in protecting the skin from UVR exposure. The present study aims to evaluate the photoprotective and antiaging efficacy of a red orange extract (100 mg/day) in both Asian and Caucasian subjects. A randomized, double-blind, controlled study was carried out in 110 Asian and Caucasian subjects. Product efficacy was measured as follows: (1) the photoprotective effect was measured by the minimal erythema dose (MED) assessment; (2) the efficacy in decreasing the UVA+B-induced skin redness was measured by colorimetry; (3) the antioxidant efficacy was measured by the ferric-reducing antioxidant power (FRAP) and the malondialdehyde (MDA) assay; and (4) skin moisturization, skin elasticity, skin radiance, the intensity of melanin staining, transepidermal water loss (TEWL), and wrinkles were measured to assess the antiaging efficacy. The intake of the product for 56 days was effective in improving the skin reaction to UV exposure; in increasing the skin antioxidant capacity as well as in decreasing UVA-induced lipid peroxidation; in increasing the skin moisturization, skin elasticity, and skin radiance; and in decreasing TEWL, the intensity of melanin staining inside dark spots, and wrinkle depth. Our results suggest that the test product is effective in counteracting both the harmful effects of UVR exposure and aging signs.

Orobanche crenata Forssk. Extract Affects Human Breast Cancer Cell MCF-7 Survival and Viral Replication.

BACKGROUND: Breast cancer (BC) is the leading cause of death worldwide. The severity of BC strictly depends on the molecular subtype. The less aggressive hormone-positive subtype is treated with adjuvant endocrine therapy (AET), which causes both physical and psychological side effects. This condition strongly impacts the adherence and persistence of AET among oncologic patients. Moreover, viral infections also constitute a serious problem for public health. Despite their efficacy, antiviral agents present several therapeutic limits. Accordingly, in the present work, we investigated the antitumor and antiviral activities of Orobanche crenata Forssk. (O. crenata), a parasitic plant, endemic to the Mediterranean basin, traditionally known for its beneficial properties for human health. METHODS: The MTT assay was carried out to evaluate the cytotoxic effect of O. crenata leaf extract (OCLE) on human breast cancer cells (MCF-7 and MDA-MB-231) and the primary HFF-1 cell line. The lactic dehydrogenase (LDH) assay was performed on MCF-7 cells to analyze necrotic cell death. The antioxidant effect of OCLE was evaluated by intracellular determination of the reactive oxygen species and thiol groups, by DPPH and ABTS assays. The antiviral activity of OCLE was determined against Poliovirus 1, Echovirus 9, Human respiratory syncytial virus, Adenovirus type 2 and type 5, Coxsackievirus B1 (CoxB1) and B3 (CoxB3), Herpes simplex type 1 (HSV-1) and type 2 (HSV-2), and ß-Coronavirus by the plaque reduction assay. RESULTS: The extract, after 24 h of incubation, did not affect MDA-MB-231 and HFF-1 cell viability. However, at the same time point, it showed a dose-dependent inhibitory effect on MCF-7 cells, with an increase in LDH release. OCLE exhibited free radical scavenging activity and significantly increased non-protein thiol levels in MCF-7 cells. OCLE effectively inhibited HSV-1, HSV-2, CoxB1, and CoxB3 replication. CONCLUSIONS: The overall results showed an interesting inhibitory effect of OCLE on both MCF-7 cell survival and viral replication.

Phytocomplex of a Standardized Extract from Red Orange (Citrus sinensis L. Osbeck) against Photoaging.

Excessive exposure to solar radiation is associated with several deleterious effects on human skin. These effects vary from the occasional simple sunburn to conditions resulting from chronic exposure such as skin aging and cancers. Secondary metabolites from the plant kingdom, including phenolic compounds, show relevant photoprotective activities. In this study, we evaluated the potential photoprotective activity of a phytocomplex derived from three varieties of red orange (Citrus sinensis (L.) Osbeck). We used an in vitro model of skin photoaging on two human cell lines, evaluating the protective effects of the phytocomplex in the pathways involved in the response to damage induced by UVA-B. The antioxidant capacity of the extract was determined at the same time as evaluating its influence on the cellular redox state (ROS levels and total thiol groups). In addition, the potential protective action against DNA damage induced by UVA-B and the effects on mRNA and protein expression of collagen, elastin, MMP1, and MMP9 were investigated, including some inflammatory markers (TNF-α, IL-6, and total and phospho NFkB) by ELISA. The obtained results highlight the capacity of the extract to protect cells both from oxidative stress­preserving RSH (p < 0.05) content and reducing ROS (p < 0.01) levels­and from UVA-B-induced DNA damage. Furthermore, the phytocomplex is able to counteract harmful effects through the significant downregulation of proinflammatory markers (p < 0.05) and MMPs (p < 0.05) and by promoting the remodeling of the extracellular matrix through collagen and elastin expression. This allows the conclusion that red orange extract, with its strong antioxidant and photoprotective properties, represents a safe and effective option to prevent photoaging caused by UVA-B exposure.

Effectiveness of "Moro" Blood Orange Citrus sinensis Osbeck (Rutaceae) Standardized Extract on Weight Loss in Overweight but Otherwise Healthy Men and Women-A Randomized Double-Blind Placebo-Controlled Study.

This study aimed to assess the efficacy of a blood orange Citrus sinensis standardized extract from "Moro" cultivar, on weight loss in overweight but otherwise healthy individuals. Anthocyanins and particularly cyanidin 3-glucoside, found in a large variety of fruits including Sicilian blood oranges, can help to counteract weight gain and to reduce body fat accumulation through the modulation of antioxidant, anti-inflammatory and metabolic pathways. In this randomized, double blind, placebo-controlled study, all participants (overweight adults aged 20−65 years old) were randomized to receive either Moro blood orange standardized extract or a placebo daily for 6-months. The primary outcome measure was change in body mass and body composition at the end of the study. After 6-months, body mass (4.2% vs. 2.2%, p = 0.015), body mass index (p = 0.019), hip (3.4 cm vs. 2.0 cm, p = 0.049) and waist (3.9 cm vs. 1.7 cm, p = 0.017) circumferences, fat mass (p = 0.012) and fat distribution (visceral and subcutaneous fat p = 0.018 and 0.006, respectively) were all significantly better in the extract supplemented group compared to the placebo (p < 0.05). In addition, all safety markers of liver toxicity were within the normal range throughout the study for both analyzed groups. Concluding, the present study demonstrates that Moro blood orange standardized extract may be a safe and effective option for helping with weight loss when used in conjunction with diet and exercise.

Effect of Protocatechuic Acid Ethyl Ester on Biomembrane Models: Multilamellar Vesicles and Monolayers.

The interactions of drugs with cell membranes are of primary importance for several processes involved in drugs activity. However, these interactions are very difficult to study due to the complexity of biological membranes. Lipid model membranes have been developed and used to gain insight into drug-membrane interactions. In this study, the interaction of protocatechuic acid ethyl ester, showing radical-scavenging activity, antimicrobial, antitumor and anti-inflammatory effects, with model membranes constituted by multilamellar vesicles and monolayers made of DMPC and DSPC, has been studied. Differential scanning calorimetry and Langmuir-Blodgett techniques have been used. Protocatechuic acid ethyl ester interacted both with MLV and monolayers. However, a stronger interaction of the drug with DMPC-based model membranes has been obtained. The finding of this study could help to understand the protocatechuic acid ethyl ester action mechanism.

Protocatechuic Acid, a Simple Plant Secondary Metabolite, Induced Apoptosis by Promoting Oxidative Stress through HO-1 Downregulation and p21 Upregulation in Colon Cancer Cells.

Gastrointestinal cancers, particularly colorectal cancer, are mainly influenced by the dietary factor. A diet rich in fruits and vegetables can help to reduce the incidence of colorectal cancer thanks to the phenolic compounds, which possess antimutagenic and anticarcinogenic properties. Polyphenols, alongside their well-known antioxidant properties, also show a pro-oxidative potential, which makes it possible to sensitize tumor cells to oxidative stress. HO-1 combined with antioxidant activity, when overexpressed in cancer cells, is involved in tumor progression, and its inhibition is considered a feasible therapeutic strategy in cancer treatment. In this study, the effects of protocatechuic acid (PCA) on the viability of colon cancer cells (CaCo-2), annexin V, LDH release, reactive oxygen species levels, total thiol content, HO-1, γ-glutamylcysteine synthetase, and p21 expression were evaluated. PCA induced, in a dose-dependent manner, a significantly reduced cell viability of CaCo-2 by oxidative/antioxidant imbalance. The phenolic acid induced modifications in levels of HO-1, non-proteic thiol groups, γ-glutamylcysteine synthetase, reactive oxygen species, and p21. PCA induced a pro-oxidant effect in cancer cells, and the in vitro pro-apoptotic effect on CaCo-2 cells is mediated by the modulation of redox balance and the inhibition of the HO-1 system that led to the activation of p21. Our results suggest that PCA may represent a useful tool in prevention and/or therapy of colon cancer.

Phytochemical Analysis and Anti-Inflammatory and Anti-Osteoarthritic Bioactive Potential of Verbascum thapsus L. (Scrophulariaceae) Leaf Extract Evaluated in Two In Vitro Models of Inflammation and Osteoarthritis.

Osteoarthritis (OA) is a complex disease, source of pain and disability that affects millions of people worldwide. OA etiology is complex, multifactorial and joint-specific, with genetic, biological and biomechanical components. Recently, several studies have suggested a potential adjuvant role for natural extracts on OA progression, in terms of moderating chondrocyte inflammation and following cartilage injury, thus resulting in an overall improvement of joint pain. In this study, we first analyzed the phenylethanoid glycosides profile and the total amount of polyphenols present in a leaf aqueous extract of Verbascum thapsus L. We then investigated the anti-inflammatory and anti-osteoarthritic bioactive potential of the extract in murine monocyte/macrophage-like cells (RAW 264.7) and in human chondrocyte cells (HC), by gene expression analysis of specifics inflammatory cytokines, pro-inflammatory enzymes and metalloproteases. Six phenylethanoid glycosides were identified and the total phenolic content was 124.0 ± 0.7 mg gallic acid equivalent (GAE)/g of extract. The biological investigation showed that the extract is able to significantly decrease most of the cellular inflammatory markers, compared to both control cells and cells treated with Harpagophytum procumbens (Burch.) DC. ex Meisn, used as a positive control. Verbascum thapsus leaf aqueous extract has the potential to moderate the inflammatory response, representing an innovative possible approach for the inflammatory joint disease treatment.

Anti-adipogenic and anti-oxidant effects of a standardised extract of Moro blood oranges (Citrus sinensis (L.) Osbeck) during adipocyte differentiation of 3T3-L1 preadipocytes.

Particular features in the pulp of blood oranges are marked levels of anthocyanin, a class of polyphenolic compounds well known to exert numerous health-promoting actions on human wellbeing including anti-obesity effects. In this study, we investigated in vitro, the antioxidant and anti-adipogenic activities of Morosil®, a standardised extract of Moro blood oranges. During adipocyte differentiation, 3T3-L1 cells were treated with concentrations of extract containing 2.5, 5, 10, 25 µM of anthocyanins. After seven days of treatment and differentiation, we measured reactive oxygen species production, non-proteic thiol groups content, adipokine secretion and triglyceride accumulation together with mRNA expression of adipogenic transcription factors such as PPARγ, C/EBPα, SREBP-1c. Furthermore, both ACCα, FAS protein expression and citrate synthase activity were measured. Results show that Morosil® exerts antioxidant and anti-adipogenic activities during adipocyte differentiation of 3T3-L1 pre-adipocytes.

Plant-Based Bioactive Molecules in Improving Health and Preventing Lifestyle Diseases.

The Special Issue, "Plant-Based Bioactive Molecules in Improving Health and Preventing Life-style Diseases", includes original research papers and reviews, which aim to increase knowledge of the molecular mechanisms underlying multiple biological effects of natural compounds from plants, responsible for maintaining human health and improving many diseases caused by people's daily lifestyles [...].

Plant Species of Sub-Family Valerianaceae-A Review on Its Effect on the Central Nervous System.

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.

A standardized extract of Opuntia ficus-indica (L.) Mill and Olea europaea L. improves gastrointestinal discomfort: A double-blinded randomized-controlled study.

Gastrointestinal discomfort (GD), which often includes gastroesophageal reflux disease (GERD), is a common disorder in healthy adults affecting 40% of the worldwide population. The symptoms related to GD can have a negative impact on the quality of life (QoL). Current treatments for GERD are associated with side effects. We conducted a randomized double-blind placebo-controlled trial to assess the effect of a standardized extract of Opuntia ficus-indica L. cladodes and Olea europaea L. leaves on the symptoms and QoL of healthy adults with GD. One hundred healthy participants with GD were enrolled in the study and divided into two groups: 60 participants taking verum (400 mg/day) and 40 taking the placebo for 8 weeks. The Gastrointestinal Quality of Life index (GIQLI) and GERD Symptom Assessment Scale (GSAS) questionnaires were administered at the beginning of the study and after 4 and 8 weeks. The group treated with verum experienced a statistically significant improvement of GIQLI and GSAS scores (p < .001). Moreover, the effect size measured revealed a clinical significance. A day-dependent improvement of symptoms was also observed. The standardized extract represents a fast, effective, and well-tolerated treatment for improving symptoms related to GD and GERD.

Antimicrobial, Antioxidant, and Cytotoxic Activities of Juglans regia L. Pellicle Extract.

The difficulty to treat resistant strains-related hospital-acquired infections (HAIs) promoted the study of phytoextracts, known sources of bioactive molecules. Accordingly, in the present study, the pharmacological activities of Juglans regia (L.) pellicle extract (WPE) were investigated. The antiviral effect was tested against Herpes simplex virus type 1 and 2, Poliovirus 1, Adenovirus 2, Echovirus 9, Coxsackievirus B1 through the plaque reduction assay. The antibacterial and antifungal activities were evaluated against medically important strains, by the microdilution method. DPPH and superoxide dismutase (SOD)s-like activity assays were used to determine the antioxidant effect. Besides, the extract was screened for cytotoxicity on Caco-2, MCF-7, and HFF1 cell lines by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also evaluated. Interestingly, WPE inhibited Herpes simplex viruses (HSVs) replication, bacterial and fungal growth. WPE showed free radical scavenging capacity and inhibited superoxide anion formation in a dose-dependent manner. These effects could be attributed to the high content of phenols and flavonoids, which were 0.377 ± 0.01 mg GE/g and 0.292 ± 0.08 mg CE/g, respectively. Moreover, WPE was able to reduce Caco-2 cell viability, at both 48 h and 72 h. The promising results encourage further studies aimed to better elucidate the role of WPE in the prevention of human infectious diseases.