scholarly journals Enzymatic Production of 3-OH Phlorizin, a Possible Bioactive Polyphenol from Apples, by Bacillus megaterium CYP102A1 via Regioselective Hydroxylation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1327
Author(s):  
Ngoc Anh Nguyen ◽  
Ngoc Tan Cao ◽  
Thi Huong Ha Nguyen ◽  
Jung-Hwan Ji ◽  
Gun Su Cha ◽  
...  
Keyword(s):  
Bacillus Megaterium ◽  
Water Solubility ◽  
Apple Tree ◽  
Inhibitory Effect ◽  
Efficient Synthesis ◽  
Chemical Methods ◽  
Enzymatic Production ◽  
Promising Agent ◽  
Potent Inhibitory Effect ◽  
Regioselective Hydroxylation

Phlorizin is the most abundant glucoside of phloretin from the apple tree and its products. Phlorizin and its aglycone phloretin are currently considered health-beneficial polyphenols from apples useful in treating hyperglycemia and obesity. Recently, we showed that phloretin could be regioselectively hydroxylated to make 3-OH phloretin by Bacillus megaterium CYP102A1 and human P450 enzymes. The 3-OH phloretin has a potent inhibitory effect on differentiating 3T3-L1 preadipocytes into adipocytes and lipid accumulation. The glucoside of 3-OH phloretin would be a promising agent with increased bioavailability and water solubility compared with its aglycone. However, procedures to make 3-OH phlorizin, a glucoside of 3-OH phloretin, using chemical methods, are not currently available. Here, a biocatalytic strategy for the efficient synthesis of a possibly valuable hydroxylated product, 3-OH phlorizin, was developed via CYP102A1-catalyzed regioselective hydroxylation. The production of 3-OH phlorizin by CYP102A1 was confirmed by HPLC and LC–MS spectroscopy in addition to enzymatic removal of its glucose moiety for comparison to 3-OH phloretin. Taken together, in this study, we found a panel of mutants from B. megaterium CYP102A1 could catalyze regioselective hydroxylation of phlorizin to produce 3-OH phlorizin, a catechol product.

scholarly journals Regioselective Hydroxylation of Naringin Dihydrochalcone to Produce Neoeriocitrin Dihydrochalcone by CYP102A1 (BM3) Mutants

Catalysts ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 823 ◽  
Author(s):  
Thi Huong Ha Nguyen ◽  
Su-Min Woo ◽  
Ngoc Anh Nguyen ◽  
Gun-Su Cha ◽  
Soo-Jin Yeom ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Bacillus Megaterium ◽  
Major Product ◽  
Artificial Sweetener ◽  
Citrus Fruits ◽  
Efficient Synthesis ◽  
Chemical Methods ◽  
Potential Applications ◽  
Regioselective Hydroxylation ◽  
Total Turnover

Naringin dihydrochalcone (DC) is originally derived from the flavonoid naringin, which occurs naturally in citrus fruits, especially in grapefruit. It is used as an artificial sweetener with a strong antioxidant activity with potential applications in food and pharmaceutical fields. At present, enzymatic and chemical methods to make products of naringin DC by hydroxylation reactions have not been developed. Here, an enzymatic strategy for the efficient synthesis of potentially valuable products from naringin DC, a glycoside of phloretin, was developed using Bacillus megaterium CYP102A1 monooxygenase. The major product was identified to be neoeriocitrin DC by NMR and LC-MS analyses. Sixty-seven mutants of CYP102A1 were tested for hydroxylation of naringin DC to produce neoeriocitrin DC. Six mutants with high activity were selected to determine the kinetic parameters and total turnover numbers (TTNs). The kcat value of the most active mutant was 11 min−1 and its TTN was 315. The productivity of neoeriocitrin DC production increased up to 1.1 mM h−1, which corresponds to 0.65 g L−1 h−1. In this study, we achieved a regioselective hydroxylation of naringin DC to produce neoeriocitrin DC.

scholarly journals Aquatic Toxicity of Photocatalyst Nanoparticles to Green Microalgae Chlorella vulgaris

Water ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 77
Author(s):  
Cristina Adochite ◽  
Luminita Andronic
Keyword(s):  
Chlorella Vulgaris ◽  
Advanced Oxidation Process ◽  
Growth Parameters ◽  
Aquatic Toxicity ◽  
Basal Medium ◽  
Inhibitory Effect ◽  
Synthesis Methods ◽  
Potent Inhibitory Effect ◽  
Density Surface ◽  
The Impact

In the last years, nanoparticles such as TiO2, ZnO, NiO, CuO and Fe2O3 were mainly used in wastewater applications. In addition to the positive aspects concerning using nanoparticles in the advanced oxidation process of wastewater containing pollutants, the impact of these nanoparticles on the environment must also be investigated. The toxicity of nanoparticles is generally investigated by the nanomaterials’ effect on green algae, especially on Chlorella vulgaris. In this review, several aspects are reviewed: the Chlorella vulgaris culture monitoring and growth parameters, the effect of different nanoparticles on Chlorella vulgaris, the toxicity of photocatalyst nanoparticles, and the mechanism of photocatalyst during oxidative stress on the photosynthetic mechanism of Chlorella vulgaris. The Bold basal medium (BBM) is generally recognized as an excellent standard cultivation medium for Chlorella vulgaris in the known environmental conditions such as temperature in the range 20–30 °C and light intensity of around 150 μE·m2·s−1 under a 16/8 h light/dark cycle. The nanoparticles synthesis methods influence the particle size, morphology, density, surface area to generate growth inhibition and further algal deaths at the nanoparticle-dependent concentration. Moreover, the results revealed that nanoparticles caused a more potent inhibitory effect on microalgal growth and severely disrupted algal cells’ membranes.

scholarly journals An Anti-Inflammatory 2,4-Cyclized-3,4-Secospongian Diterpenoid and Furanoterpene-Related Metabolites of a Marine Sponge Spongia sp. from the Red Sea

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 38
Author(s):  
Chi-Jen Tai ◽  
Chiung-Yao Huang ◽  
Atallah F. Ahmed ◽  
Raha S. Orfali ◽  
Walied M. Alarif ◽  
...  
Keyword(s):  
Red Sea ◽  
Superoxide Anion ◽  
Dermal Fibroblast ◽  
Fibroblast Cell ◽  
Inhibitory Effect ◽  
Human Dermal Fibroblast ◽  
Superoxide Anion Generation ◽  
Potent Inhibitory Effect ◽  
Anti Inflammatory ◽  
New Compounds

Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone (1), a carboxylic acid, spongiafuranic acid A (2), one hydroxamic acid, spongiafuranohydroxamic acid A (3), and a furanyl trinorsesterpenoid 16-epi-irciformonin G (4), along with three known metabolites (−)-sponalisolide B (5), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one (6), and cholesta-7-ene-3β,5α-diol-6-one (7). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 μM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

Mobilization of Fibrinogen Receptor Sites on Human Platelets Stimulated with ADP is Prevented by Prostacyclin

1979 ◽  
Author(s):  
J. Hawiger ◽  
S. Parkinson ◽  
S. Timmons
Keyword(s):  
Inhibitory Effect ◽  
Human Platelets ◽  
Affinity Constant ◽  
Human Fibrinogen ◽  
Fibrinogen Receptor ◽  
Receptor Sites ◽  
Plasma Factor ◽  
Potent Inhibitory Effect

Fibrinogen is a plasma factor required for aggregation of human platelets by ADP. The mechanism of platelet-ADP-fibrinogen interaction was studied by measuring the equilibrium binding of 125I-fibrinogen to human platelets separated from plasma proteins. Binding of 125I-fibrinogen to platelets not stimulated with ADP was low and unaffected by an excess of unlabel led fibrinogen. However, when platelets were stimulated with 4μM of ADP, there was an eightfold increase In the number of available binding sites for human fibrinogen, with affinity constant of 1.9 x 109M-1. This striking increase in fibrinogen receptor sites on human platelets was specific for ADP as contrasted to ATP, AMP, and adenosine. Prostacyclin (Prostaglandin I2, PGI2), a novel prostaglandin produced by the blood vessel wall, completely blocked this ADP-induced increase in fibrinogen receptor sites on human platelets. The effect of PGI2 was prompt and concentration dependent, reaching maximum at 10-9M. 6-keto PGF2 a stable derivative ot PGI2, did not have such an effect. Thus movement of fibrinogen receptor sites on human platelet membrane stimulated with ADP is prevented by PGI2. This represents a new biologic property of this vascular hormone and contributes to better understanding of its potent inhibitory effect in vitro and in vivo on ADP-induced platelet aggregation requiring mobilization of fibrinogen receptor.

scholarly journals α-Lipoic Acid Potentiates the Anti-Inflammatory Activity of Avocado/Soybean Unsaponifiables in Chondrocyte Cultures

Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Carmelita G. Frondoza ◽  
Lowella V. Fortuno ◽  
Mark W. Grzanna ◽  
Stacy L. Ownby ◽  
Angela Y. Au ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Nuclear Factor Kappa B ◽  
Nuclear Translocation ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Chondrocyte Cultures ◽  
Potent Inhibitory Effect ◽  
Anti Inflammatory ◽  
Pharmacologic Treatments

Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) control media, (2) ASU, (3) LA, or (4) ASU + LA combination. Cells were activated with lipopolysaccharide (LPS), interleukin 1β (IL-1β) or hydrogen peroxide (H2O2) for 24 hours and supernatants were immunoassayed for PGE2. Nuclear factor-kappa B (NF-κB) analyses were performed by immunocytochemistry and Western blot following 1 hour of activation with IL-1β. Results LPS, IL-1β, or H2O2 significantly increased PGE2 production. ASU or LA alone suppressed PGE2 production in LPS and IL-1β activated cells. Only LA alone at 2.5 µg/mL was inhibitory in H2O2-activated chondrocytes. ASU + LA inhibited more than either agent alone in all activated cells. ASU + LA also inhibited the IL-1β induced nuclear translocation of NF-κB. Conclusions The present study provides evidence that chondrocyte PGE2 production can be inhibited by the combination of ASU + LA more effectively than either ASU or LA alone. Inhibition of PGE2 production is associated with the suppression of NF-κB translocation. The potent inhibitory effect of ASU + LA on PGE2 production could offer a potential advantage for a combination anti-inflammatory/antioxidant approach in the management of OA.

scholarly journals Rooibos tea extracts inhibit osteoclast formation and activity through the attenuation of NF-κB activity in RAW264.7 murine macrophages

2018 ◽  
Vol 9 (6) ◽  
pp. 3301-3312 ◽  
Author(s):  
Shaakirah Moosa ◽  
Abe E. Kasonga ◽  
Vishwa Deepak ◽  
Sumari Marais ◽  
Innocentia B. Magoshi ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Murine Macrophages ◽  
Rooibos Tea ◽  
Potent Inhibitory Effect ◽  
Inhibit Osteoclast Formation

Fermented rooibos extract has more potent inhibitory effect on osteoclasts than unfermented rooibos.

scholarly journals Saccharomonosporine A inspiration; synthesis of potent analogues as potential PIM kinase inhibitors

RSC Advances ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 6752-6762
Author(s):  
Asmaa M. AboulMagd ◽  
Hossam M. Hassan ◽  
Ahmed M. Sayed ◽  
Usama Ramadan Abdelmohsen ◽  
Hamdy M. Abdel-Rahman
Keyword(s):  
Kinase Inhibitors ◽  
Inhibitory Effect ◽  
Potent Inhibitory Effect

The E isomer of compound 5 exhibited a potent inhibitory effect against PIM kinase isoforms of IC50s 0.30–0.41 μM.

Potent inhibitory effect of alpha-viniferin on human cytochrome P450

2014 ◽  
Vol 69 ◽  
pp. 276-280 ◽  
Author(s):  
Juhee Sim ◽  
Hae Wring Jang ◽  
Min Song ◽  
Ji Hyang Kim ◽  
Seung Ho Lee ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Inhibitory Effect ◽  
Human Cytochrome ◽  
Potent Inhibitory Effect

scholarly journals The molecular basis of mouse sperm–zona pellucida binding: a still unresolved issue in developmental biology

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 377-381 ◽  
Author(s):  
Gary F Clark
Keyword(s):  
Zona Pellucida ◽  
Molecular Basis ◽  
Three Dimensional ◽  
Inhibitory Effect ◽  
Specific Model ◽  
Cell Stage ◽  
Sperm Binding ◽  
Potent Inhibitory Effect ◽  
Alternate Model ◽  
Sperm Plasma Membrane

During murine fertilization, sperm bind to the specialized extracellular matrix of the egg, known as the zona pellucida (ZP). This matrix is composed of three major glycoproteins designated ZP1, ZP2, and ZP3. Three models for sperm–ZP binding are now under consideration. The domain-specific model posits that adhesion relies primarily on interactions between N-glycans located within the C-terminal domain of ZP3 and a lectin-like egg-binding protein in the sperm plasma membrane. However, this model does not explain recent results obtained in studies with ZP2mut mice. In the supramolecular structure model, sperm bind to a three-dimensional zona matrix that depends on the cleavage status of ZP2. This paradigm does not explain the potent inhibitory effect of specific carbohydrate sequences or a C-terminal glycopeptide (gp55) derived from ZP3. Recently, O-glycans linked at Thr155 and Thr162 of ZP3 were implicated as potential ligands that mediate initial sperm–ZP binding. This novel model will be reviewed. A major challenge is to develop an alternate model for sperm–ZP binding that fits as much of the data as possible. Such a model is presented in this review. This paradigm could explain how the inability to cleave ZP2mut in ZP2mut mice could result in continued sperm binding to two-cell stage embryos without the formation of a supramolecular binding complex. These novel insights should guide future experiments that will eventually determine the molecular basis underlying gamete binding in the mouse and other eutherian mammals.

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