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) Gramnegative 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-β 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

Interest of 3-arylcoumarins as xanthine oxidase inhibitors

The 19th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural Products ChemistryIn the current paper we studied the interest of a series of 3-arylcoumarin derivatives as xanthine oxidase inhibitors. For the best compound of the series, the 4’-methoxyphenyl-6-nitrocoumarin, it was determined the IC50 value and the type of inhibition. This work is a preliminary screening for further design and synthetize new non-purinergic derivatives as potential compounds involved in the inflammatory suppression, specially related to the gou

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

Butyrylcholinesterase Inhibitors: Structure-Activity Relationships of 2-Phenylbenzofuran derivatives.

Butyrylcholinesterase Inhibitors: Structure-Activity Relationships of 2-Phenylbenzofuran derivatives Antonella Fais1*, Giovanna L. Delogu 1, Benedetta Era 1, Amalia Di Petrillo1, Amit Kumar2,3, Paola Caria4, Sonia Floris1, Francesca Pintus1 1Department of Life and Environmental Sciences, University of Cagliari , Cagliari , Italy; 2Department of Mech., Chem. and Material Engineering , University of Cagliari , Cagliari , Italy; 3Biosciences Sector, CRS4 ,Pula , Italy 4Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy *Corresponding author: [email protected] Alzheimer’s disease (AD) is an irreversible and progressive brain disorder which is characterized by progressive memory loss and a wide range of cognitive impairments.1 Although the precise cause of AD is not completely known, there are some factors that seem to play a significant role in the pathogenesis of AD. Since AD is characterized by a forebrain cholinergic neuron loss and a progressive decline in acetylcholine, a possible therapeutic strategy involves the use of cholinesterase (ChE) inhibitors to restore the neurotransmitter level and thus alleviate AD symptoms.2 Benzofuran scaffold has drawn considerable attention over the last few years due to its profound physiological and chemotherapeutic properties. Recent studies have also investigated their inhibitory activity towards ChEs.3,4 In this study, a series of 2-phenylbezonfurans compounds were synthesized and their inhibition activity towards the ChE enzymes were investigated. We further combined biochemical analysis and molecular modelling studies to identify selective butyrylcholinesterase (BChE) inhibition by benzofuran scaffold. In particular, two compounds exhibited the highest BChE inhibition with IC50 values better than the standard cholinesterase inhibitor compound. Molecular modelling studies highlighted the importance of catalytic and peripheral site residues in BChE inhibition. Subsequently, the biosafety of the two promising compounds was evaluated, in NSC-34 cells at the concentration in which BChE activity is inhibited, and no considerable cytotoxic effect was found. References 1. Schuster et al. Bioorg. Med. Chem. (2010) 18, 5071. 2. Zemek et al. Expert Opin Drug Saf (2014) 13, 759. 3. Mostofi et al. Eur. J. Med. Chem. (2015) 103, 361. 4. Delogu et al. Bioorg. Med. Chem. (2016) 26, 2308

Tyrosinase inhibition and antioxidant properties of Asphodelus microcarpus extracts

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

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

Evaluation of antioxidant and tyrosinase inhibitory activities ofthe 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 nhexane 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-Oglucuronide, 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

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

Interest of 3-arylcoumarins as xanthine oxidase inhibitors

In the current paper we studied the interest of a series of 3-arylcoumarin derivatives as xanthine oxidase inhibitors. For the best compound of the series, the 4'-methoxyphenyl-6-nitrocoumarin, it was determined the IC50 value and the type of inhibition. This work is a preliminary screening for further design and synthetize new non-purinergic derivatives as potential compounds involved in the inflammatory suppression, specially related to the gout

Study of a series of 8-substitued 7-hydroxy-4-methylcoumarins as AChE and BuChE inhibitors

In the current work we studied the interest of a series of 8-substitued 7-hydroxy-4-methylcoumarins as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. For the best compounds of the series, the IC50 value was determined. This work was based on previous results and is a preliminary screening for further design and synthesis of new derivatives as potential compounds that can modulate enzymatic systems involved in the neurodegenerative diseases