scholarly journals PB28, the Sigma-1 and Sigma-2 Receptors Modulator With Potent Anti–SARS-CoV-2 Activity: A Review About Its Pharmacological Properties and Structure Affinity Relationships

2020 ◽  
Vol 11 ◽  
Author(s):  
Carmen Abate ◽  
Mauro Niso ◽  
Francesca Serena Abatematteo ◽  
Marialessandra Contino ◽  
Nicola Antonio Colabufo ◽  
...  
Keyword(s):  
Biological Properties ◽  
Sigma Receptor ◽  
In Vitro Assays ◽  
Receptor Subtypes ◽  
Cardiac Side Effects ◽  
Receptor Modulator ◽  
Sigma 1 ◽  
Human Proteins ◽  
Speed Up

These unprecedented times have forced the scientific community to gather to face the COVID-19 pandemic. Efforts in diverse directions have been made. A multi-university team has focused on the identification of the host (human) proteins interacting with SARS-CoV-2 viral proteins, with the aim of hampering these interactions that may cause severe COVID-19 symptoms. Sigma-1 and sigma-2 receptors surprisingly belong to the “druggable” host proteins found, with the pan-sigma receptor modulator PB28 displaying the most potent anti–SARS-CoV-2 activity in in vitro assays. Being 20-fold more active than hydroxychloroquine, without cardiac side effects, PB28 is a promising antiviral candidate worthy of further investigation. Our research group developed PB28 in 1996 and have thoroughly characterized its biological properties since then. Structure–affinity relationship (SAfiR) studies at the sigma receptor subtypes were also undertaken with PB28 as the lead compound. We herein report our knowledge of PB28 to share information that may help to gain insight into the antiviral action of this compound and sigma receptors, while providing structural hints that may speed up the translation into therapeutics of this class of ligands.

scholarly journals Anti-Inflammatory Effects of Formononetin 7-O-phosphate, a Novel Biorenovation Product, on LPS-Stimulated RAW 264.7 Macrophage Cells

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3910 ◽  
Author(s):  
Min-Seon Kim ◽  
Jin-Soo Park ◽  
You Chul Chung ◽  
Sungchan Jang ◽  
Chang-Gu Hyun ◽  
...  
Keyword(s):  
Biological Properties ◽  
In Vitro Assays ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Macrophage Cells ◽  
Anti Inflammatory ◽  
Reduced Toxicity

Biorenovation is a microbial enzyme-catalyzed structural modification of organic compounds with the potential benefits of reduced toxicity and improved biological properties relative to their precursor compounds. In this study, we synthesized a novel compound verified as formononetin 7-O-phosphate (FMP) from formononetin (FM) using microbial biotransformation. We further compared the anti-inflammatory properties of FMP to FM in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. We observed that cell viabilities and inhibitory effects on LPS-induced nitric oxide (NO) production were greater in FMP-treated RAW 264.7 cells than in their FM-treated counterparts. In addition, FMP treatment suppressed the production of proinflammatory cytokines such as prostaglandin-E2 (PGE2), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner and concomitantly decreased the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). We also found that FMP exerted its anti-inflammatory effects through the downregulation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa B (NF-κB) signaling pathways. In conclusion, we generated a novel anti-inflammatory compound using biorenovation and demonstrated its efficacy in cell-based in vitro assays.

Novel pan sigma receptor modulator exerts strong apoptotic effect in in vitro primary 3D-cell cultures of human glioblastoma

2016 ◽  
Vol 69 ◽  
pp. S146-S147
Author(s):  
S. Pignatta ◽  
C. Arienti ◽  
M. Zanoni ◽  
A. Zamagni ◽  
S. Collina ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Sigma Receptor ◽  
Human Glioblastoma ◽  
Receptor Modulator ◽  
3D Cell Cultures ◽  
Apoptotic Effect

scholarly journals Serotonin modifies cytoskeleton and brush-border membrane architecture in human intestinal epithelial cells

2008 ◽  
Vol 295 (4) ◽  
pp. G700-G708 ◽  
Author(s):  
Ravinder K. Gill ◽  
Le Shen ◽  
Jerrold R. Turner ◽  
Seema Saksena ◽  
Waddah A. Alrefai ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Brush Border ◽  
Brush Border Membrane ◽  
In Vitro Assays ◽  
Receptor Subtypes ◽  
Ion Transporters ◽  
Cortical Actin ◽  
Intracellular Ca ◽  
Membrane Architecture

Serotonin or 5-hydroxytryptamine (5-HT) influences numerous functions in the gastrointestinal tract. We previously demonstrated that 5-HT treatment of Caco-2 cells inhibited Na+/H+ exchangers (NHE) and Cl−/OH− exchange activities via distinct signaling mechanisms. Since regulation of several ion transporters such as NHE3 is influenced by intact cytoskeleton, we hypothesized that 5-HT modifies actin cytoskeleton and/or brush-border membrane architecture via involvement of signaling pathways. Ultrastructural analysis showed that 5-HT (0.1 μM, 1 h) treatment of Caco-2 cells caused the apical membrane to assume a convex dome shape that was associated with shortening of microvilli. To examine whether these cellular architecture changes are cytoskeleton driven, we analyzed actin cytoskeleton by fluorescence microscopy. 5-HT induced basal stress fibers with prominent cortical actin filaments via 5-HT3 and 5-HT4 receptor subtypes. This induction was partially attenuated by chelation of intracellular Ca2+ and PKCα inhibition (Go6976). In vitro assays revealed that PKCα interacted with actin and this association was increased by 5-HT. Our data provide novel evidence that 5-HT-induced signaling via 5-HT3/4 receptor subtypes to cause Ca2+ and PKCα-dependent regulation of actin cytoskeleton may play an important role in modulation of ion transporters that contribute to pathophysiology of diarrheal conditions associated with elevated levels of 5-HT.

scholarly journals Evaluation of the Cytopathicity (Fusion/Hemifusion) of Patient-Derived HIV-1 Envelope Glycoproteins Comparing Two Effector Cell Lines

2012 ◽  
Vol 17 (6) ◽  
pp. 727-737 ◽  
Author(s):  
Francesc Cunyat ◽  
Marta Curriu ◽  
Silvia Marfil ◽  
Elisabet García ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
Cell Death ◽  
Single Cell ◽  
Cell Lines ◽  
Effector Cell ◽  
Cell Loss ◽  
Biological Properties ◽  
In Vitro Assays ◽  
Envelope Glycoproteins ◽  
Hiv 1

HIV-1 envelope glycoprotein (Env) is a major determinant of viral pathogenicity. The evaluation of the biological properties of patient-derived envelopes by comparing two effector cell lines (293T and HeLa) is reported. A standard cell-to-cell fusion assay was used to evaluate fusogenicity, whereas a coculture with CD4+ cells was used to evaluate absolute cell loss, single cell death, and hemifusion events. Fusion and absolute cell loss assays showed that Env-expressing 293T and HeLa cells had different fusion efficiencies; fusion was magnified in 293T cells despite a significantly lower cell-surface Env expression. Conversely, gp41-mediated single cell death and hemifusion induced in CD4+ cells by 293T-Env-positive cells were significantly lower than that induced by HeLa-Env-positive cells. These data showed that the effector cell line used in the in vitro assays is crucial, and a combination of assays is recommended to evaluate the biological properties of patient-derived envelope glycoproteins: preferentially, 293T-Env-positive cells for the evaluation of fusogenicity and HeLa-Env-positive cells for the evaluation of cell death parameters. The combination of assays described in our work could be a valuable tool for dual screenings of large collections of primary Envs or Env mutants and drugs acting on these Envs.

scholarly journals Potential Health Benefits of Origanum heracleoticum Essential Oil: Phytochemical and Biological Variability among Different Calabrian Populations

2018 ◽  
Vol 13 (9) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Mariangela Marrelli ◽  
Fabrizio Araniti ◽  
Maria Rosa Abenavoli ◽  
Giancarlo Statti ◽  
Filomena Conforti
Keyword(s):  
Essential Oils ◽  
Health Benefits ◽  
Hierarchical Cluster ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
In Vitro Assays ◽  
No Production ◽  
Potential Health ◽  
Phytochemical Content

The potential health benefits of the essential oils of six different populations of Origanum heracleoticum L. from Calabria (Italy) were assessed, together with the evaluation of the influence of the site of collection on their metabolic profile and biological activity. Different terpenoids were identified, being thymol, carvacrol and o-cymene among the most abundant ones. Hierarchical cluster analysis allowed the identification of two main groups, which were discriminated by the altitude of collection. The antioxidant activity was tested by means of two in vitro assays: DPPH and β-carotene bleaching test. Samples EO-4 and EO-3 were the most active in protecting linoleic acid from peroxidation, with IC50 values of 4.00 and 4.68 μg/mL after 30 minutes of incubation. The anti-inflammatory potential was assessed through the evaluation of the capacity to inhibit NO production in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cell line. All essential oils induced a dose-depending inhibitory effect. An excellent activity was demonstrated for sample EO-4, followed by sample EO-3 (IC50 values equal to 32.77 and 49.48 μg/mL, respectively). Observed biological properties were correlated to the phytochemical content of analyzed samples.

scholarly journals Multicriteria Optimization of Phenolic Compounds Capture from a Sunflower Protein Isolate Production Process by-Product by Adsorption Column and Assessment of Their Antioxidant and Anti-Inflammatory Effects

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 760
Author(s):  
Tuong Thi Le ◽  
Armelle Ropars ◽  
Arnaud Aymes ◽  
Jean-Pol Frippiat ◽  
Romain Kapel
Keyword(s):  
Phenolic Compounds ◽  
Flow Rate ◽  
Multicriteria Optimization ◽  
Radical Scavenging ◽  
Biological Properties ◽  
Protein Isolate ◽  
In Vitro Assays ◽  
Necrosis Factor Alpha ◽  
Sunflower Protein

The aim of this study was to valorize liquid effluent from the sunflower protein isolate process by extracting phenolic compounds it contains. To do so, XAD7 resin was used. A multicriteria optimization methodology based on design of experiments showed the optimal conditions were adsorption flow rate of 15 BV/h at pH 2.7, a desorption flow rate at 120 BV/h with ethanol/water 50% (v/v). The best trade-off between purity and recovery yields resulted in the production of a fraction containing 76.05% of chlorogenic acid (CGA) whose biological properties were evaluated. DPPH and ABTS tests showed that this fraction had a higher radical scavenging capacity than vitamin C. In vitro assays have shown that this fraction, when used at a concentration corresponding to 50 or 100 µM of CGA, does not present any cytotoxicity on human THP-1 cells differentiated into macrophages. In addition, this fraction when added prior to the inflammatory stimulus (LPS) can reduce tumor necrosis factor-alpha (TNF-α) production by 22%, thereby highlighting its protective properties against future inflammation.

scholarly journals Redesigning Arenicin-1, an Antimicrobial Peptide from the Marine Polychaeta Arenicola marina, by Strand Rearrangement or Branching, Substitution of Specific Residues, and Backbone Linearization or Cyclization

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 376 ◽  
Author(s):  
Dmitriy S. Orlov ◽  
Olga V. Shamova ◽  
Igor E. Eliseev ◽  
Maria S. Zharkova ◽  
Oleg B. Chakchir ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Mammalian Cells ◽  
Structural Features ◽  
Biological Properties ◽  
In Vitro Assays ◽  
Gram Positive ◽  
Gram Negative ◽  
Arenicola Marina ◽  
Dynamics Simulations

Arenicin-1, a β-sheet antimicrobial peptide isolated from the marine polychaeta Arenicola marina coelomocytes, has a potent, broad-spectrum microbicidal activity and also shows significant toxicity towards mammalian cells. Several variants were rationally designed to elucidate the role of structural features such as cyclization, a certain symmetry of the residue arrangement, or the presence of specific residues in the sequence, in its membranolytic activity and the consequent effect on microbicidal efficacy and toxicity. The effect of variations on the structure was probed using molecular dynamics simulations, which indicated a significant stability of the β-hairpin scaffold and showed that modifying residue symmetry and β-strand arrangement affected both the twist and the kink present in the native structure. In vitro assays against a panel of Gram-negative and Gram-positive bacteria, including drug-resistant clinical isolates, showed that inversion of the residue arrangement improved the activity against Gram-negative strains but decreased it towards Gram-positive ones. Variants with increased symmetry were somewhat less active, whereas both backbone-cyclized and linear versions of the peptides, as well as variants with R→K and W→F replacement, showed antimicrobial activity comparable with that of the native peptide. All these variants permeabilized both the outer and the inner membranes of Escherichia coli, suggesting that a membranolytic mechanism of action was maintained. Our results indicate that the arenicin scaffold can support a considerable degree of variation while maintaining useful biological properties and can thus serve as a template for the elaboration of novel anti-infective agents.

Conformational and Biological Properties of Partial Sequences of Glucagon

1973 ◽  
Vol 51 (4) ◽  
pp. 243-248 ◽  
Author(s):  
Richard M. Epand ◽  
Vijaylaxmi Grey
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Biological Properties ◽  
In Vitro Assays ◽  
Adenyl Cyclase Activity ◽  
Amino Acid Fragment ◽  
Acid Fragment ◽  
Carboxyl Terminal ◽  
Derivatives Of

We have investigated the properties of derivatives of the 29-amino-acid polypeptide hormone, glucagon, which had varying numbers of amino acids cleaved from the carboxyl terminal portion of the molecule. These derivatives included a 27-amino-acid fragment made by cleavage of the native molecule with cyanogen bromide and a 23-amino-acid fragment made synthetically. We found both of these derivatives capable of stimulating the conversion of ATP to cyclic AMP in in vitro assays using rat liver homogenates. The concentration of these peptides, which were required to produce enhanced adenyl cyclase activity, was higher than that of glucagon, and in the case of the 1–23 derivative it was several orders of magnitude larger. The requirement for higher concentrations of peptide is expected, as removal of a large portion of the total number of amino acids will proportionately decrease the free energy of dissociation of the peptide from the membrane receptor, thus changing the equilibrium constant for binding by several orders of magnitude. Circular dichroism and ultra-centrifuge studies of these peptides, as well as a 21-amino-acid fragment made by cleavage of the native molecule with carboxypeptidase, indicated that the shorter glucagon analogues have structures similar to that of the native molecule although somewhat less ordered.

scholarly journals Prunus spinosa L. leaf extracts: polyphenol profile and bioactivities

2021 ◽  
Vol 49 (1) ◽  
pp. 12137
Author(s):  
Ivona VELIČKOVIĆ ◽  
Željko ŽIŽAK ◽  
Nemanja RAJČEVIĆ ◽  
Marija IVANOV ◽  
Marina SOKOVIĆ ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
Ethanol Extract ◽  
Biological Properties ◽  
Acetone Extract ◽  
In Vitro Assays ◽  
Aqueous Sample ◽  
Leaf Extracts ◽  
Antitumor Effects ◽  
Prunus Spinosa

Prunus spinosa leaf extracts in solvents of different polarity (water, ethanol and acetone), their phenol, flavonoid and anthocyanin contents and biological properties were the object of this study. The richest in phenols as well as in flavonoids was acetone extract with 181.19 mg GAE and 80.10 mg QE per gram of dry extract, respectively. Moreover, the quantity of anthocyanins obtained by HPLC analysis was also the highest in acetone sample. Examined samples possessed antioxidant properties evaluated through four in vitro assays (DPPH, ABTS, FRAP and TRC). The acetone extract was proved to be the best antioxidant among tested samples, which could be ascribed to polyphenols, especially anthocyanins. The aqueous and the ethanol extract exhibited antibacterial effects, being particularly active against B. cereus and E. cloacae. T. viride, P. funiculosum, P. ochrochloron, P. verrucosum var. cyclopium were the most susceptible among fungal microorganisms examined. Both, the aqueous and the ethanol extract expressed inhibitory activity towards enzymes linked to diabetes mellitus type II. Additionally, the ethanol extract showed significantly higher potential in inhibiting α-glucosidase than the drug used as the positive control. Furthermore, the aqueous sample revealed antitumor effects on following malignant cell lines: HeLa, K562 and MDA-MB-453. The results presented herein suggest that P. spinosa leaves should be considered as a natural source of bioactive compounds with potential application in phytopharmacy and food industry.

scholarly journals Screening of Antioxidant Potentials and Bioactive Properties of the Extracts Obtained from Two Centaurea L. Species (C. kroumirensis Coss. and C. sicula L. subsp sicula)

2020 ◽  
Vol 10 (7) ◽  
pp. 2267 ◽  
Author(s):  
Nedra Dhouibi ◽  
Simona Manuguerra ◽  
Rosaria Arena ◽  
Abdelkarim Mahdhi ◽  
Concetta Maria Messina ◽  
...  
Keyword(s):  
Total Phenolic Content ◽  
Phenolic Content ◽  
Radical Scavenging ◽  
Herbal Medicines ◽  
Reducing Power ◽  
Biological Properties ◽  
In Vitro Assays ◽  
Total Phenolic ◽  
Human Skin Fibroblast

Herbal medicines, dietary supplements, or infusions with health promoting effects can note strong consumer demand. Hence, researchers and scientists have been increasingly focusing on the promotion of medicinal plants. In this respect, the present study has the evaluation of the biological properties of different extracts (hexane, chloroform, methanol, ultrasonic, essential oil, and supercritical) obtained from two Centaurea species (C. kroumirensis (Coss.) and C. sicula L. subsp sicula) as purpose. Antioxidative activities were assessed by in vitro assays including total phenolic content, free radical scavenging assay and ferric ion reducing power. Among the fourteen extracts examined, the highest total phenolic content (TPC) and antioxidant abilities were recorded in ultrasonic ethanol extracts of both Centaurea species. Additionally, these extracts exhibited a noticeable strong protective effect of the human skin fibroblast cell line (HS-68) that was exposed to oxidative stress induced by hydrogen peroxide. According to our results, the sonication with ethanol might be an ideal, rapid, and eco-friendly extraction method for obtaining a polyphenol-rich extract that exhibited high antioxidant activity. The results presented herein suggest that Centaurea species could be promoted as an antioxidant resource that could be exploited for the development of nutraceuticals or in pharmacology industry.

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