Pistacia lentiscus: Phytochemistry and Antidiabetic Properties.

Pistacia lentiscus L. (P. lentiscus) is an evergreen shrub (Anacardiaceae family) primarily found in the Mediterranean region. The plant has been thoroughly characterized, resulting in a high concentration of bioactive compounds as flavonoids and phenolics. Moreover, P. lentiscus was revealed to possess a great nutritional and industrial importance because of its variety of biological activities, including antibacterial, anti-inflammatory, anti-atherogenic and antioxidant properties. Many of its beneficial health properties and applications date back to antiquity, and the European Medicines Agency officially acknowledged it as an herbal medicinal product. Indeed, it is widely employed in conventional medicine to treat several diseases, including type 2 diabetes (T2D). On this basis, this review aims to summarize and describe the chemical composition of different parts of the plant and highlight the potential of P. lentiscus, focusing on its antidiabetic activities. The plant kingdom is drawing increasing attention because of its complexity of natural molecules in the research of novel bioactive compounds for drug development. In this context, P. lentiscus demonstrated several in vitro and in vivo antidiabetic effects, acting upon many therapeutic T2D targets. Therefore, the information available in this review highlighted the multitarget effects of P. lentiscus and its great potential in T2D treatment.

Exploring Asphodelus microcarpus as a source of xanthine oxidase inhibitors: Insights from in silico and in vitro studies.

Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects. Our study focuses on Asphodelus microcarpus, a plant renowned for traditional anti-inflammatory uses. Recent investigations into its phenolic-rich flowers, notably abundant in luteolin derivatives, reveal its potential as a natural source of XO inhibitors. In the present research, XO inhibition by an ethanolic flowers extract from A. microcarpus is reported. In silico docking studies have highlighted luteolin derivatives as potential XO inhibitors, and molecular dynamics support that luteolin 7-O-glucoside has the highest binding stability compared to other compounds and controls. In vitro studies confirm that luteolin 7-O-glucoside inhibits XO more effectively than the standard inhibitor allopurinol, with an IC50 value of 4.8 µg/mL compared to 11.5 µg/mL, respectively. These findings underscore the potential therapeutic significance of A. microcarpus in managing conditions related to XO activity. The research contributes valuable insights into the health-promoting properties of A. microcarpus and its potential application in natural medicine, presenting a promising avenue for further exploration in disease management.

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice.

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

Inhibitory Effect of Quercetin on Oxidative Endogen Enzymes: A Focus on Putative Binding Modes.

Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by anti-oxidant defense systems. Cells can produce ROS during physiological processes, but excessive ROS can lead to non-specific and irreversible damage to biological molecules, such as DNA, lipids, and proteins. Mitochondria mainly produce endogenous ROS during both physiological and pathological conditions. Enzymes like nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO), and monoamine oxidase (MAO) contribute to this process. The body has enzymatic and non-enzymatic defense systems to neutralize ROS. The intake of bioactive phenols, like quercetin (Que), can protect against pro-oxidative damage by quenching ROS through a non-enzymatic system. In this study, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its anti-oxidant properties. Que can act as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups. Additionally, it can effectively inhibit the activity of several endogenous oxidative enzymes by binding them with high affinity and specificity. Que had the best molecular docking results with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Que's binding to these enzymes was confirmed by subsequent molecular dynamics, revealing different stability phases depending on the enzyme bound. The 500 ns simulation showed a net evolution of binding for NOX and MPO. These findings suggest that Que has potential as a natural therapy for diseases related to oxidative stress.

Nanoparticles in Cancer Diagnosis and Treatment.

The use of tailored medication delivery in cancer treatment has the potential to increase efficacy while decreasing unfavourable side effects. For researchers looking to improve clinical outcomes, chemotherapy for cancer continues to be the most challenging topic. Cancer is one of the worst illnesses despite the limits of current cancer therapies. New anticancer medications are therefore required to treat cancer. Nanotechnology has revolutionized medical research with new and improved materials for biomedical applications, with a particular focus on therapy and diagnostics. In cancer research, the application of metal nanoparticles as substitute chemotherapy drugs is growing. Metals exhibit inherent or surface-induced anticancer properties, making metallic nanoparticles extremely useful. The development of metal nanoparticles is proceeding rapidly and in many directions, offering alternative therapeutic strategies and improving outcomes for many cancer treatments. This review aimed to present the most commonly used nanoparticles for cancer applications.

GPR120/FFAR4: A Potential New Therapeutic Target for Inflammatory Bowel Disease.

Inflammatory bowel disease, whose major forms are Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gut due to the loss of tolerance toward antigens normally contained in the gut lumen. G protein-coupled receptor (GPR) 120 has gained considerable attention as a potential therapeutic target for metabolic disorders due to its implication in the production of the incretin hormone glucagon-like peptide 1 and the secretion of cholecystokinin. Recent studies have also highlighted the role of GPR120 in regulating immune system activity and inflammation. GPR120, expressed by intestinal epithelial cells, proinflammatory macrophages, enteroendocrine L cells, and CD4+ T cells, suppresses proinflammatory and enhances anti-inflammatory cytokine production, suggesting that GPR120 might have a pivotal role in intestinal inflammation and represent a possible therapeutic target in inflammatory bowel disease. This narrative review aims at summarizing the role of GPR120 in the maintenance of intestinal homeostasis through the analysis of the most recent studies.

Quercetin and its derivates as antiviral potentials: A comprehensive review.

Quercetin, widely distributed in fruits and vegetables, is a flavonoid known for its antioxidant, antiviral, antimicrobial, and antiinflammatory properties. Several studies highlight the potential use of quercetin as an antiviral, due to its ability to inhibit the initial stages of virus infection, to be able to interact with proteases important for viral replication, and to reduce inflammation caused by infection. Quercetin could also be useful in combination with other drugs to potentially enhance the effects or synergistically interact with them, in order to reduce their side effects and related toxicity. Since there is no comprehensive compilation about antiviral activities of quercetin and derivates, the aim of this review is providing a summary of their antiviral activities on a set of human viral infections along with mechanisms of action. Thus, the following family of viruses are examined: Flaviviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Hepadnaviridae, Retroviridae, Picornaviridae, Pneumoviridae, and Filoviridae.

Chemical composition and enzyme inhibition of Phytolacca dioica L. seeds extracts.

Phytolacca, which belongs to the family of Phytolaccaceae, are known for their use in popular medicine. Bioactivity of five extracts from Phytolacca dioica seeds were evaluated in four bioassays. A selected group of compounds from the extract that displayed the best bioactivity was analysed. The ethyl acetate extract (EAE) possessed the highest content of phenolics, the highest inhibitory activity on the tyrosinase and xanthine oxidase enzymes and showed a high antioxidant activity. HPLC-DAD-MS was employed to identify the phenolics profile of the most active one (EAE). HSCCC analysis of the EAE led to the isolation of phytolaccoside B and a mixture of 4 isomers, isoamericanol B1, B2, C1 and C2. These isoamericanol isomers presented activity against tyrosinase and xanthine oxidase. Our results revealed for the first time an interesting biological activity of the extract and isolated compounds from P. dioica seeds, which could be considered as a source of bioactive molecules.

Sardinian honeys as sources of xanthine oxidase and tyrosinase inhibitors.

Sardinian honeys obtained from different floral sources (Arbutus, Asphodelus, Eucalyptus, Thistle, and Sulla) were evaluated for their ability to inhibit tyrosinase and xanthine oxidase enzymes and for their antioxidant activity. Physicochemical parameters, total phenolic, and flavonoids content were also determined. Honey from Arbutus flowers had the highest antioxidant activity followed by Eucalyptus and Thistle ones. These three honeys showed good tyrosinase and xanthine oxidase inhibition properties. Thus, these Sardinian honeys could have a great potential as antioxidant sources for pharmaceutical and cosmetic applications.

Selected Enzyme Inhibitory Effects of Euphorbia characias Extracts.

Extracts of aerial part of Euphorbia characias were examined to check potential inhibitors for three selected enzymes involved in several metabolic disorders. Water and ethanol extracts from leaves and flowers showed in vitro inhibitory activity toward α-amylase, α-glucosidase, and xanthine oxidase. IC50 values were calculated for all the extracts and the ethanolic extracts were found to exert the best effect. In particular, for the α-glucosidase activity, the extracts resulted to be 100-fold more active than the standard inhibitor. The inhibition mode was investigated by Lineweaver-Burk plot analysis. E. characias extracts display different inhibition behaviors toward the three enzymes acting as uncompetitive, noncompetitive, and mixed-type inhibitors. Moreover, ethanolic extracts of E. characias showed no cytotoxic activity and exhibited antioxidant capacity in a cellular model. The LC-DAD metabolic profile was also performed and it showed that leaves and flowers extracts contain high levels of quercetin derivatives. The results suggest that E. characias could be a promising source of natural inhibitors of the enzymes involved in carbohydrate uptake disorders and oxidative stress.

Novel 2-pheynlbenzofuran derivatives as selective butyrylcholinesterase inhibitors for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder representing the leading cause of dementia and is affecting nearly 44 million people worldwide. AD is characterized by a progressive decline in acetylcholine levels in the cholinergic systems, which results in severe memory loss and cognitive impairments. Expression levels and activity of butyrylcholinesterase (BChE) enzyme has been noted to increase significantly in the late stages of AD, thus making it a viable drug target. A series of hydroxylated 2-phenylbenzofurans compounds were designed, synthesized and their inhibitory activities toward acetylcholinesterase (AChE) and BChE enzymes were evaluated. Two compounds (15 and 17) displayed higher inhibitory activity towards BChE with IC50 values of 6.23 µM and 3.57 µM, and a good antioxidant activity with EC50 values 14.9 µM and 16.7 µM, respectively. The same compounds further exhibited selective inhibitory activity against BChE over AChE. Computational studies were used to compare protein-binding pockets and evaluate the interaction fingerprints of the compound. Molecular simulations showed a conserved protein residue interaction network between the compounds, resulting in similar interaction energy values. Thus, combination of biochemical and computational approaches could represent rational guidelines for further structural modification of these hydroxy-benzofuran derivatives as future drugs for treatment of AD.

Broad-range potential of Asphodelus microcarpus leaves extract for drug development.

BACKGROUND: Many plants have been used in traditional medicine for their antibacterial, antifungal, antiprotozoal, antiviral, antidiarrhoeal, analgesic, antimalarial, antioxidant, anti-inflammatory and anticancer activities. In order to find novel antimicrobial and antiviral agents, the aim of the present study was the evaluation of the antibacterial and antibiofilm susceptibility of Asphodelus microcarpus leaves extract. Moreover, the antiviral activity and the phytochemical composition of the active extract were also determined. METHODS: Antimicrobial and antibiofilm activities of leaves ethanol extract of A. microcarpus were evaluated on 13 different microbial strains. We selected three different sets of microorganisms: (i) Gram-positive bacteria, (ii) Gram-negative bacteria and (iii) yeasts. The potential antiviral activity of A. microcarpus leaves ethanol extract was evaluated with a luciferase reporter gene assay in which the dsRNA-dependent RIG-I-mediated IFN-ß activation was inducted or inhibited by the Ebola virus VP35 protein. HPLC-DAD-MS was used to identify phenolic profile of the active extract. RESULTS: A. microcarpus leaves extract showed a potent inhibitory activity on Gram-positive bacteria while only a reduced inhibition was observed on Gram-negative bacteria. No activity was detected against Yeasts. The extract also showed an interesting antibiofilm motif on various bacterial strains (E. coli, S. aureus, S. haemolyticus and B. clausii). Moreover, this extract significantly affected the Ebola virus VP35 inhibition of the viral RNA (vRNA) induced IFN response. CONCLUSIONS: The overall results provide supportive data on the use of A. microcarpus as antimicrobial agent and a potential source of anti-viral natural products. Data collected set the bases for further studies for the identification of single active components and the development of new pharmaceuticals.

Evaluation of antioxidant and tyrosinase inhibitory activities of the extracts of Sarcopoterium spinosum (L.) Spach fruits.

Sarcopoterium spinosum fruits have been used to get extracts of different nature; two fixed oils were obtained by means of supercritical fluid extraction (SFE) with CO2 at 250 bar and 40°C and using n-hexane in a Soxhlet extraction (SE) apparatus. Aqueous solutions: an aromatic water (AW) and a residual water (RW) were obtained by hydrodistillation (HD). In the RW, following have been identified: quercetin glucuronide, luteolin 7-O-glucuronide, isorhamnetin 3-O-glucuronide, quercetin sulfate and quercetin. Among all tested plant extracts, the RW had the highest content of polyphenol (378 mg GAE/g of weight) and of flavonoids (26 mg QE/g of weight), and the highest antioxidant activity, comparable to that of Trolox. It was also the most active extract of this series (IC50 = 0.292 mg/mL) in the tyrosinase activity assays performed with L-3,4-dihydroxyphenylalanine (L-DOPA) as substrate.

New insights into highly potent tyrosinase inhibitors based on 3-heteroarylcoumarins: Anti-melanogenesis and antioxidant activities, and computational molecular modeling studies.

Melanogenesis is a physiological pathway for the formation of melanin. Tyrosinase catalyzes the first step of this process and down-regulation of its activity is responsible for the inhibition of melanogenesis. The search for molecules capable of controlling hyperpigmentation is a trend topic in health and cosmetics. A series of heteroarylcoumarins have been synthesized and evaluated. Compounds 4 and 8 exhibited higher tyrosinase inhibitory activities (IC50=0.15 and 0.38µM, respectively), than the reference compound, kojic acid (IC50=17.9µM). Compound 4 acts as competitive, while compound 8 as uncompetitive inhibitor of mushroom tyrosinase. Furthermore, compounds 2 and 8 inhibited tyrosinase activity and melanin production in B16F10 cells. In addition, compounds 2-4 and 8 proved to have an interesting antioxidant profile in both ABTS and DPPH radicals scavenging assays. Docking experiments were carried out in order to study the interactions between these heteroarylcoumarins and mushroom tyrosinase.

Tyrosinase inhibition and antioxidant properties of Asphodelus microcarpus extracts.

BACKGROUND: Asphodelus microcarpus belongs to the family Liliaceae that include several medicinal plants. In the traditional medicine plants of the genus Asphodelus are used to treat skin disorders such as ectodermal parasites, psoriasis, microbial infection and for lightening freckles. In order to find novel skin depigmenting agents, the present work was carry out to evaluate antioxidant activity and tyrosinase inhibitory potential of leaves, flowers and tubers extracts of A. microcarpus. The phytochemical composition of the active extract was also evaluated. METHODS: Three different extracts (water, methanol and ethanol) from leaves, flowers and tubers of A. microcarpus were evaluated for their inhibitory effect on tyrosinase activity using L-3,4-dihydroxyphenylalanine (L-DOPA) as substrate. Inhibition of cellular tyrosinase activity and melanin production was also investigated in melanoma B16F10 cells. Antioxidant activity, total phenolic and flavonoids contents were determined using standard in vitro methods. HPLC-DAD-MS was used to identify phenolic profile of the active extract. RESULTS: The results showed that all extracts have a direct inhibitory anti-tyrosinase activity, with ethanolic extract from flowers (FEE) exhibiting the stronger effect. Kinetic analysis revealed that FEE acts as an uncompetitive inhibitor with a Ki value of 0.19 mg/mL. The same effect was observed in murine melanoma B16F10 cells. Cellular tyrosinase activity as well as melanin content were reduced in FEE-treated cells. The results were comparable to that of the standard tyrosinase inhibitor (kojic acid). Furthermore, the same extract showed the highest antioxidant activity and an elevated levels of total phenolics and flavonoid content. Eleven phenolic components were identified as chlorogenic acid, luteolin derivates, naringenin and apigenin. CONCLUSIONS: Our findings showed that FEE from A. microcarpus inhibits tyrosinase and exerted antimelanogenesis effect in B16F10 cells. This extract also showed the highest scavenging activity, which could be mainly attributed to its high levels of total polyphenols and flavonoids. These results suggest that A. microcarpus has a great potential as sources of bioactive compounds which could be used as depigmenting agents in skin disorders.

A novel malate dehydrogenase from Ceratonia siliqua L. seeds with potential biotechnological applications.

A novel malate dehydrogenase (MDH; EC 3.1.1.1.37), hereafter MDHCs, from Ceratonia siliqua seeds, commonly known as Carob tree, was purified by using ammonium sulphate precipitation, ion exchange chromatography on SteamLine SP and gel-filtration. The molecular mass of the native protein, obtained by analytical gel-filtration, was about 65 kDa, whereas, by using SDS-PAGE analysis, with and without reducing agent, was 34 kDa. The specific activity of purified MDHCs (0.25 mg/100 g seeds) was estimated to be 188 U/mg. The optimum activity of the enzyme is at pH 8.5, showing a decrease in the presence of Ca(2+), Mg(2+) and NaCl. The N-terminal sequence of the first 20 amino acids of MDHCs revealed 95 % identity with malate dehydrogenase from Medicago sativa L. Finally, the enzymatic activity of MDHCs was preserved even after absorption onto a PVDF membrane. To our knowledge, this is the first contribution to the characterization of an enzyme from Carob tree sources.