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1.
ACS Omega ; 9(14): 16701-16715, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617634

RESUMO

Since the emergence of SARS-CoV-2 in 2020, the world has faced a global pandemic, emphasizing the urgent need for effective treatments to combat COVID-19. This study explores the use of green-synthesized carbon-based nanomaterials as potential inhibitors of ACE2, a critical receptor for SARS-CoV-2 entry into host cells. Specifically, the study examines four carbon-based nanomaterials, namely, CD1, CD2, CD3, and CD4 in amino, graphitic, pyridinic, and pyrrolic forms, respectively, synthesized from curcumin, to investigate their binding affinity with ACE2. Molecular docking studies revealed that CD3 (pyridinic form) exhibited the highest binding affinity with ACE2, surpassing that of the control compound, curcumin. Notably, CD3 formed hydrophobic interactions and hydrogen bonds with key ACE2 residues, suggesting its potential to block the binding of SARS-CoV-2 to human cells. Moreover, molecular dynamics simulations demonstrated the stability of these ligand-ACE2 complexes, further supporting the promise of CD3 as an inhibitor. Quantum chemical analyses, including frontier molecular orbitals, natural bond orbital analysis, and the quantum theory of atoms in molecules, unveiled valuable insights into the reactivity and interaction strengths of these ligands. CD3 exhibited desirable chemical properties, signifying its suitability for therapeutic development. The study's findings suggest that green-synthesized carbon-based nanomaterials, particularly CD3, have the potential to serve as effective inhibitors of ACE2, offering a promising avenue for the development of treatments against COVID-19. Further experimental validation is warranted to advance these findings and establish new therapies for the ongoing global pandemic.

2.
Chem Pharm Bull (Tokyo) ; 72(2): 220-225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38382975

RESUMO

CeO2 nanoparticles (nanoceria) were proposed as an alternative physical sunscreen agent with antioxidant properties and comparable UV absorption performance. Green synthesis of nanoceria with Ag and Ni dopants resulted in doped nanoceria with lower catalytic activity and biologically-safe characteristics. The doped nanoceria was characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Rancimat Instrument, and UV-Vis Spectrophotometer for SPF (Sun Protection Factor) determination. XRD and TEM analysis showed that nanoceria had been successfully formed in nanoscale-sized with a change in crystallite size due to the crystal defect phenomenon caused by dopant addition. While the Rancimat test and band gap energy analysis were conducted to evaluate the oxidative stability and reactive oxygen species formation, it was confirmed that dopant addition could decrease catalytic activity of material, resulting in Ni-doped Ce with a longer incubation time (11.81 h) than Ag-doped Ce (10.58 h) and non-doped Ce (10.30 h). In-vitro SPF value was measured using the thin layer technique of sunscreen prototype with Virgin Coconut Oil (VCO)-based emulsion, which yielded 10.862 and 5.728 SPF values for 10% Ag-doped Ce and 10% Ni-doped Ce, respectively. The dopant addition of nanoceria could reduce catalytic activity and give a decent in vitro UV-shielding performance test; thus, Ag and Ni-doped nanoceria could be seen as promising candidates for alternative physical sunscreen agents.


Assuntos
Cério , Nanopartículas , Protetores Solares/farmacologia , Espécies Reativas de Oxigênio , Nanopartículas/química , Cério/farmacologia , Cério/química
3.
ACS Appl Bio Mater ; 7(1): 114-123, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38096155

RESUMO

Precise visualization of biological processes necessitates reliable coloring technologies, and fluorescence imaging has emerged as a powerful method for capturing dynamic cellular events. Low emission intensity and solubility of intrinsic fluorescence are still challenging, hindering their application in the biomedical field. The nanostructurization and functionalization of the insoluble phytochemicals, such as chlorophyll and curcumin, into carbon dots (CDs) were conducted to address these challenges. Due to their unique fluorescence characteristics and biocompatibility, CDs derived from medicinal plants hold promise as bioimaging agents. Further, the nitrogen in situ functionalization of the as-synthesized CDs offered tunable optical properties and enhanced solubility. The surface modification aims to achieve a more positive zeta potential, facilitating penetration through biological membranes. This work provides valuable insights into utilizing functionalized phytochemical-embedded carbon dots for bioimaging applications. The doping of nitrogen by adding urea showed an alteration of surface charge, which is more positive based on zeta potential measurement. The more positive CD particles showed that Andrographis paniculata-urea-based CDs were the best particles to penetrate cells than others related to the alteration of the surface charge and the functional group of the CDs, with the optimum dose of 12.5 µg/mL for 3 h of treatment for bioimaging assay.


Assuntos
Plantas Medicinais , Pontos Quânticos , Pontos Quânticos/química , Carbono/química , Nitrogênio/química , Ureia
4.
Chem Biol Drug Des ; 103(1): e14365, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37749066

RESUMO

A mannose-binding protein from the mushroom Agaricus bisporus (Abmb) inhibits the growth of MDA-MB-231 cells, which is of an aggressive breast cancer subtype. This ability was observed in a monolayer cell (2D) culture setup, which often is unable to capture changes in cell morphology, polarity and division. That shortcoming may overestimate Abmb potency for its development as a pharmaceutical agent and its use in a therapy. Hence, Abmb's inhibition to the cell growth was performed in the 3D cell (spheroid) culture, which is more representative to the situation in vivo. The result showed that, although the presence of Abmb at ~14.7 µM already disrupted the MDA-MB-231 cell morphology in the 2D culture, its presence at ~16.5 µM only ceased the growth of the MDA-MB-231 spheroid. Further, Abmb is unique because structurally it belongs to the R-type lectin (RTL) family; most of mannose-binding protein is of the C-type lectin (CTL). As the natural ligand of Abmb is unknown thus the mechanism of action is unclear, Abmb effect on the cancer cells was assessed via observation of the altered expression of genes involved in the Wnt/ß-catenin signalling, which is one of the canonical pathways in the proliferation of cancer cells. The results suggested that Abmb did not alter the pathway upon exerting its anti-proliferative activity to the MDA-MB-231 cells.


Assuntos
Agaricus , Neoplasias da Mama , Lectina de Ligação a Manose , Humanos , Feminino , Lectina de Ligação a Manose/farmacologia , Lectinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proliferação de Células , Linhagem Celular Tumoral
5.
Proteome Sci ; 21(1): 8, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37158880

RESUMO

BACKGROUND: Lumbrokinase derived from earthworms, Lumbricus rubellus is known to have fibrinolytic enzymes that have potential as therapeutic drugs due to its ability to dissolve fibrin. The current study is aimed to purify the Lumbrokinase from L. rubellus and identify its protein component. METHODS: Water extract of local earthworm Lumbricus rubellus revealed several proteins. Therefore, to identify its protein component, purification through HiPrep DEAE fast flow and proteomic analysis were conducted prior to identifications. A combination of two-dimension gel electrophoresis (2DE) and electrospray ionization mass spectrometry analysis was used to identify the purified fractions. RESULTS: The purified fractions contain five protein bands, namely F25-1, F25-2, F85-1, F85-2, and F85-3, which displayed strong fibrinogenolytic activity. F25 fractions showed fibrinogenolytic activity of 974.85 U/mg, while F85 fractions showed higher activity of 1,484.11 U/mg. Fractions F85-1, F85-2, and F85-3 showed molecular weights of 42.6 kDa, 27.03 kDa, and 14 kDa, respectively and were identified as Lumbrokinase iso-enzymes. CONCLUSION: This preliminary study indicates that the F25 and F85 fractions are similar to published fibrinolytic protease-1 and lumbrokinase, respectively, in terms of their amino acid sequence.

6.
Pharm Nanotechnol ; 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37165592

RESUMO

AIM: The present study aims to produce a novel therapeutic approach for the treatment of photoaging. BACKGROUND: Plant-derived exosome-like nanoparticles (PDENs) are nano-sized vesicles containing biomolecules released by multivesicular bodies. Recently, studies have shown the efficacy of exosomes in treating photoaging through increasing collagen synthesis and decreasing collagen degradation. In addition, some PDENs were also proven to contain bioactive metabolites, which also have potential antioxidant activity to mitigate the risk of photoaging. OBJECTIVE: Formulating and developing a gel and incorporating it with exosomes derived from golden cherry (Physalis minima). METHOD: The formulation was developed by first preparing various base formulations with different compositions and selecting the best through evaluation tests. The results showed that only polymer base natrosol with a concentration of 0.25% was suitable for incorporating exosomes. The selected base was then incorporated with various concentrations of golden cherry exosomes and was evaluated regarding its physical and stability profile. RESULT: The result demonstrates that the incorporated gel displayed pleasant organoleptic properties and a pH compatible with the skin, with pseudoplastic flow and a suitable viscosity for topical application. The stability study also only revealed minor changes in viscosity and pH without affecting the general stability of the formulation. Formulation incorporating 0.25% golden cherry exosomes had shown the best stability profile compared to other concentrations. On characterization, although the incorporated exosomes showed heterogeneous particle size distribution (PI > 0.3), they still maintained their structural integrity. In addition, the incorporated exosomes showed antioxidant activity with IC 50 of 372.435 µg/mL, which can help mitigate the risk of photoaging. CONCLUSION: Golden cherry exosomes have been successfully incorporated into gel and, thus, can be potentially utilized as a novel therapeutic approach for the treatment of photoaging.

7.
Heliyon ; 9(5): e15958, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37187901

RESUMO

As one of the most popular sources for fish albumin, Channa striata has been considered as a promising substitute for human albumin. However, scientific information regarding its genomic and proteomic is very limited, making its identification rather complicated. In this study, we aimed to isolate, characterize, and examine the bioactivity of protein and peptide derivatives of C. striata albumin. Fractionation of albumin from C. striata extract was conducted using Cohn Process and the yield was evaluated. The peptides were further produced by enzymatic hydrolysis. All these proteins were studied using tricine-SDS PAGE and tested for in vitro ACE inhibition. Dry weights of the Fraction-5, where the albumin was more abundant and purer, was 3.8 ± 2.1%. Based on tricine-SDS PAGE analysis, two bands of protein, e.g., approximately 10 and 13 kDa, were detected with highest intensity found in Fraction-5, which might be albumin of C. striata. An increasing trend of ACE inhibition by the fractions was observed, ranging from 7.09 to 22.99%. The highest ACEI activity was found in peptides from alcalase hydrolysis with molecular size <3 kDa (56.65 ± 2.32%, IC50 36.93 µg/mL). This value was also statistically significant compared with the non-hydrolyzed Fraction-5 and Parental Fraction, which were 23.48 ± 3.11% (P < 0.05) and 13.02 ± 0.68% (P < 0.01), respectively. Taken together, these findings suggest a promising potential of peptide-derived C. striata albumin for natural antihypertensive agents.

8.
ACS Omega ; 8(11): 10077-10085, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36969408

RESUMO

The alteration of ACE2 expression level, which has been studied in many diseases, makes the topic of ACE2 inducer potential crucial to be explored. The ACE2 inducer could further be designed to control the ACE2 expression level, which is appropriate to a specific case. An in vitro study of well-characterized carbon dots (CDs), made from citric acid and urea, was performed to determine their ability to modulate the ACE2 receptor. Gene expression of ACE2 was quantified using concentrations adjusted for IC50 results from CDs viability assays in HEK 293 and A549 cell lines. RT-qPCR was used to assess the expression of the ACE2 gene and its induction effect in normal cell lines (HEK-293A). According to the results of the tests, ACE2 is expressed in HEK-293A cell lines, and diminazene aceturate can increase ACE2 expression. The effect of CDs on ACE2 gene expression was further examined on the cell lines that had previously been induced with diminazene aceturate, which resulted in upregulation of the ACE2 expression level. An in silico study has been done by using a molecular docking approach. The molecular docking results show that CDs can make strong interactions with ACE2 amino acid residues through hydrophobic interaction, π-π interaction, π-cation interaction, and ionic interaction.

9.
Pharm Nanotechnol ; 11(2): 167-179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36330633

RESUMO

BACKGROUND: The main problem in the use of docetaxel as a potent chemotherapeutic agent is its solubility. Practically insoluble docetaxel requires a harsh formulation with high surfactant and alcohol concentrations to comply with the product quality. However, this formulation is inconvenient for patients. Polymeric micelles using a biocompatible polymer, poloxamer, seem to be a promising approach to increase the solubility of docetaxel, avoiding the high polysorbate and alcohol contents in the commercial product and yielding similar or better anticancer effects. OBJECTIVE: This study aims to investigate the effects of surfactant with three different charges on the particle size, chemical stability, in vitro drug release and anticancer efficacy of the docetaxelloaded poloxamer-based polymeric micelle formulation. METHODS: The freeze drying method was used to prepare polymeric micelles of docetaxel. Dynamic light scattering was used to determine particle size. The morphology of particles was investigated using a transmission electron microscope. High Pressure Liquid Chromatography was used to measure encapsulation efficiency, drug loading, and percentage of drug released. MTT assay was used to assess the anticancer effect. RESULTS: Nonionic and anionic surfactants tended to increase the particle size, while cationic surfactants had no effect. Furthermore, the addition of cationic surfactant increased the chemical stability of docetaxel. Poloxamer polymeric micelles have sustained drug release, and the addition of a surfactant can increase polymeric micelle drug release. All surfactant charges increased the anticancer efficacy of docetaxel compared to the commercial formulation Taxotere, except for the formulation prepared with an anionic surfactant. CONCLUSION: The charge of the surfactant affects the particle size, chemical stability, drug release and anticancer properties of docetaxel-loaded poloxamer polymeric micelles. Cationic surfactant formulations have shown to be promising, resulting in the most stable and highest anticancer effect.


Assuntos
Poloxâmero , Tensoativos , Humanos , Poloxâmero/química , Docetaxel , Micelas , Portadores de Fármacos/química , Polímeros/química
10.
Braz. J. Pharm. Sci. (Online) ; 58: e21125, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1420373

RESUMO

Abstract Poloxamer is a biocompatible polymer that has already been approved by the US FDA for multiple applications. Poloxamer itself has many grades and functional categories that enable the improvement of both physicochemical and biological properties of drugs. In this minireview, the functional properties of poloxamer for physicochemical modification, such as solubility and stability, and biological response modification, such as neuroprotection, cell apoptosis, efflux pump modification, membrane cell modification, and cellular uptake, are discussed to provide a broader understanding to assist the development of poloxamer-based formulations.

11.
Protein J ; 40(4): 554-561, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33959874

RESUMO

Agaricus bisporus mannose-binding protein (Abmb) was discovered as part of mushroom tyrosinase (PPO3) complex. Apart from its presence, nothing is known about its function or activity in the mushroom. The protein is evolutionarily related to lectins with ß-trefoil fold, which are glucose or galactose (and their derivatives) binding proteins. Abmb is also recently showed to display the typical agglutination activity of lectin when in complex with PPO3; this further supports Abmb similarity to its structural homologs from lectin with ß-trefoil fold. However, Abmb has no affinity towards glucose or galactose but for mannose, thus its binding to the sugar may be different from its homologs. To date, the natural ligand of Abmb is unknown and the structure of Abmb in the presence of a ligand is not available. Therefore, the mannose-binding site of Abmb was predicted using molecular docking, which was consulted with the information from its structural homologs. This conservative approach would prevent over-speculation. The mannose-binding site of Abmb is likely located in the same region to that of Abmb structural homologs but with a shift in position due to the presence of additional surface loop. In addition, benefiting from the information from an in vitro study on Abmb sugar specificity, the mannose poses suggested that the sugar might interact with the side chains of Arg15, Thr45, Gln48, Asp49, Asp51 and Arg51. Most of these residues were equally present in Abmb structural homologs despite variation of their positions in the amino acid sequence. The variation probably originates from alteration of its amino acid sequence during evolution.


Assuntos
Agaricus/química , Proteínas Fúngicas/química , Lectina de Ligação a Manose/química , Dobramento de Proteína , Sítios de Ligação , Conformação Proteica em Folha beta
12.
R Soc Open Sci ; 8(2): 201127, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972845

RESUMO

Density functional theory has been gaining popularity for studying the radical scavenging activity of antioxidants. However, only a few studies investigate the importance of calculation methods on the radical-scavenging reactions. In this study, we examined the significance of (i) the long-range correction on the coulombic interaction and (ii) the London dispersion correction to the hydroperoxyl radical-scavenging reaction of trans-resveratrol and gnetin C. We employed B3LYP, CAM-B3LYP, M06-2X exchange-correlation functionals and B3LYP with the D3 version of Grimme's dispersion in the calculations. The results showed that long-range correction on the coulombic interaction had a significant effect on the increase of reaction and activation energies. The increase was in line with the change of hydroperoxyl radical's orientation in the transition state structure. Meanwhile, the London dispersion correction only had a minor effect on the transition state structure, reaction energy and activation energy. Overall, long-range correction on the coulombic interaction had a significant impact on the radical-scavenging reaction.

13.
Pharm Nanotechnol ; 9(3): 210-216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33563189

RESUMO

BACKGROUND: Curcumin is a well-documented bioactive compound present in Curcuma sp., a tropical, medicinal plant. This substance exhibits broad-spectrum biological activities, including antivirus. Despite the lack of pharmaceutical properties of curcumin limits its clinical use. OBJECTIVE: This study aims to produce curcumin nanoemulsion with different surface charge (curcumin (+) nanoemulsion and curcumin (-) nanoemulsion) and to evaluate its physical characteristics, in vitro cell cytotoxicity, and antiviral activity against dengue virus (DENV) 1 and 2. METHODS: Two forms of nanoemulsion were prepared, which were differed from their surface charge through spontaneous procedure resulting in similar characteristics except for the zeta potential value. Cytotoxicity was determined using the RT-PCR method in the A549 cell line, and anti- DENV properties were determined by calculation of inhibitory concentration 50 (IC50) value. RESULTS: The positive charge of curcumin-loaded nanoemulsion showed a better effect in reducing the viral replication represented by a lower IC50 value. In addition, DENV-1 was more sensitive and responsive to curcumin as compared to DENV-2. CONCLUSION: Positive surface charge of curcumin-loaded nanoemulsion improves the antiviral effect of the curcumin, suggesting a promising approach for alternative treatment for dengue virus infection.


Assuntos
Curcumina , Células A549 , Antivirais/farmacologia , Curcumina/farmacologia , Emulsões , Humanos , Replicação Viral
14.
Curr Gene Ther ; 20(5): 383-394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33019928

RESUMO

BACKGROUND: Lipopeptide-based gene carriers have shown low cytotoxicity, are capable of cell membrane penetration, are easy to manufacture and therefore are great potential candidates for gene delivery applications. OBJECTIVES: This study aims to explore a range of short synthetic lipopeptides, (Lau: Lauryl; Pal: Palmitoyl) consisting of an alkyl chain, one cysteine (C), 1 to 2 histidine (H), and lysine (K) residues by performing in-silico molecular interaction and in-vitro evaluation. METHODS: The molecular interactions between the lipopeptides and Importin-α receptor were performed using AutoDock Vina and Amber14. The lipopeptide/DNA complexes were evaluated in- -vitro for their interactions, particle size, zeta potential and transgene expression. Transfection efficiency of the lipopeptides and Pal-CKKHH-derived liposome was carried out based on luciferase transgene expression. RESULTS: The in-silico interaction showed that Lau-CKKH and Pal-CKKHH hypothetically expedited nuclear uptake. Both lipopeptides had lower binding energy (-6.3 kcal/mol and -6.2 kcal/mol, respectively), compared to the native ligand, viz, nuclear localization sequence (-5.4 kcal/mol). The short lipopeptides were able to condense DNA molecules and efficiently form compacted nanoparticles. Based on the in-vitro evaluation on COS-7, Pal-CKKHH was found to be the best transfection agent amongst the lipopeptides. Its transfection efficiency (ng Luc/mg total protein) increased up to ~3-fold higher (1163 + 55) as it was formulated with helper lipid DOPE (1:2). The lipopeptide- based liposome (Pal-CKKHH: DOPE=1:2) also facilitated luciferase transgene expression on human embryonic kidney cells (293T) and human cervical adenocarcinoma cells (HeLa) with transfection efficiency 1779 +52 and 260 + 22, respectively. CONCLUSION: Our study for the first time has shown that the fully synthesized short lipopeptide Pal- CKKHH is able to interact firmly with the Importin-α. The lipopeptide is able to condense DNA molecules efficiently, facilitate transgene expression, expedite the nuclear uptake process, and hence has the characteristics of a potential transfection agent.


Assuntos
DNA/farmacologia , Técnicas de Transferência de Genes , Lipopeptídeos/genética , alfa Carioferinas/genética , Simulação por Computador , DNA/química , DNA/genética , Terapia Genética/tendências , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipopeptídeos/farmacologia , Lipossomos/farmacologia , Nanopartículas/química , Tamanho da Partícula , Transfecção , Transgenes/genética , alfa Carioferinas/farmacologia
15.
Int J Nanomedicine ; 15: 6433-6449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922010

RESUMO

BACKGROUND: Electrospun nanofibers based on Colocasia esculenta tuber (CET) protein are considered as a promising material for wound dressing applications. However, the use of these nanofibers in aqueous conditions has poor stability. The present study was performed to obtain insights into the crosslinked electrospun CET's protein-chitosan (CS)-poly(ethylene oxide) (PEO) nanofibers and to evaluate their potential for wound dressing applications. METHODS: The electrospun nanofibers were crosslinked with glutaraldehyde (GA) vapor and heat treatment (HT) to enhance their physicochemical stability. The crosslinked nanofibers were characterized by protein profiles, morphology structures, thermal behavior, mechanical properties, and degradation behavior. Furthermore, the antibacterial properties and cytocompatibility were analyzed by antibacterial assessment and cell proliferation. RESULTS: The protein profiles of the electrospun CET's protein-CS-PEO nanofibers before and after HT crosslinking contained one major bioactive protein with a molecular weight of 14.4 kDa. Scanning electron microscopy images of the crosslinked nanofibers indicated preservation of the structure after immersion in phosphate buffered saline. The crosslinked nanofibers resulted in higher ultimate tensile strength and lower ultimate strain compared to the non-crosslinked nanofibers. GA vapor crosslinking showed higher water stability compared to HT crosslinking. The in vitro antibacterial activity of the crosslinked nanofibers showed a stronger bacteriostatic effect on Staphylococcus aureus than on Escherichia coli. Human skin fibroblast cell proliferation on crosslinked GA vapor and HT nanofibers with 1% (w/v) CS and 2% (w/v) CET's protein demonstrated the highest among all the other crosslinked nanofibers after seven days of cell culture. Cell proliferation and cell morphology results revealed that introducing higher CET's protein concentration on crosslinked nanofibers could increase cell proliferation of the crosslinked nanofibers. CONCLUSION: These results are promising for the potential use of the crosslinked electrospun CET's protein-CS-PEO nanofibers as bioactive wound dressing materials.


Assuntos
Antibacterianos/farmacologia , Quitosana/química , Colocasia/química , Reagentes de Ligações Cruzadas/química , Nanofibras/química , Proteínas de Plantas/química , Tubérculos/química , Polietilenoglicóis/química , Animais , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nanofibras/ultraestrutura , Proteínas de Plantas/ultraestrutura , Staphylococcus aureus/efeitos dos fármacos , Estresse Mecânico , Temperatura
16.
Molecules ; 25(10)2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32443732

RESUMO

The mushroom Agaricus bisporus secretes biologically active compounds and proteins with benefits for human health. Most reported proteins from A. bisporus are tyrosinases and lectins. Lectins are of therapeutic or pharmaceutical interest. To date, only limited information is available on A. bisporus lectins and lectin-like proteins. No therapeutic products derived from A. bisporus lectin (ABL) are available on the market despite its extensive exploration. Recently, A. bisporus mannose-binding protein (Abmb) was discovered. Its discovery enriches the information and increases the interest in proteins with therapeutic potential from this mushroom. Furthermore, the A. bisporus genome reveals the possible occurrence of other lectins in this mushroom that may also have therapeutic potential. Most of these putative lectins belong to the same lectin groups as ABL and Abmb. Their relationship is discussed. Particular attention is addressed to ABL and Abmb, which have been explored for their potential in medicinal or pharmaceutical applications. ABL and Abmb have anti-proliferative activities toward cancer cells and a stimulatory effect on the immune system. Possible scenarios for their use in therapy and modification are also presented.


Assuntos
Agaricus/química , Lectinas/genética , Lectina de Ligação a Manose/genética , Monofenol Mono-Oxigenase/genética , Agaricus/genética , Genoma Fúngico/genética , Humanos , Lectinas/uso terapêutico , Lectina de Ligação a Manose/química , Lectina de Ligação a Manose/uso terapêutico , Monofenol Mono-Oxigenase/química
17.
Biochem Biophys Res Commun ; 527(4): 1027-1032, 2020 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-32439171

RESUMO

Agaricus bisporus mannose-binding protein (Abmb) was discovered as part of the mushroom tyrosinase (PPO3) complex, but its function in the mushroom has remained obscure. The protein has a ß-trefoil structure that is common for Ricin-B-like lectins. Indeed, its closest structural homologs are the hemagglutinin components of botulinum toxin (HA-33) and the Ricin-B-like lectin from Clitocybe nebularis (CNL), both of which bind galactose, and actinohivin, a recently discovered mannose-binding lectin from actinomycetes. Here we show that Abmb is evolutionarily related to them, which are lectins with a ß-trefoil fold. We also show for the first time that Abmb can exhibit typical lectin agglutination activity but only when in the complex with mushroom tyrosinase. This is unexpected and unique because the two proteins are not evolutionarily related and have different activities. Lectin and tyrosinase major role in defense mechanism as well as Abmb and PPO3 gene regulation during the early stages of the development of mushroom fruiting bodies suggested that Abmb has likely a function in defense against bacterial infection and/or insect-induced damage.


Assuntos
Agaricus/química , Proteínas Fúngicas/química , Lectinas/química , Lectina de Ligação a Manose/química , Agaricus/genética , Sequência de Aminoácidos , Proteínas Fúngicas/genética , Lectinas/genética , Lectina de Ligação a Manose/genética , Modelos Moleculares , Filogenia , Conformação Proteica em Folha beta
18.
Pharm Nanotechnol ; 8(1): 54-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31858909

RESUMO

BACKGROUND: Curcumin has been used as a traditional medicine showing antiinflammatory, antimicrobial, and antiviral properties. Despite the promising potentials, curcumin-based drug development is hindered due to its poor solubility and cell uptake. OBJECTIVE: This study aims to produce curcumin nanoemulsion (nanocurcumin) and evaluate its physical characteristics and in vitro cell cytotoxicity and antiviral activity against dengue virus (DENV). METHODS: Nanocurcumin was generated by self-nanoemulsion technique. Cytotoxicity was determined using MTT assay in A549 cell line. Anti-DENV properties were determined by calculation of inhibitory concentration 50 (IC50) and plaque assay. RESULTS: The resulting nanoemulsion showed uniform droplet size distribution with the average droplet size of 40.85 ± 0.919 nm. Nanocurcumin exhibited higher cell cytotoxicity compared to curcumin solution and may be explained by better cell uptake. Nanocurcumin treatment suppressed DENV growth, although no significant difference observed compared to the curcumin solution counterpart. Greater virus reduction was observed for DENV-1 and DENV-2. CONCLUSION: The synthesis of nanocurcumin improved curcumin physicochemical properties with potential as antiviral against DENV.


Assuntos
Antivirais/farmacologia , Curcumina/farmacologia , Vírus da Dengue/efeitos dos fármacos , Células A549 , Animais , Antivirais/química , Cápsulas , Linhagem Celular , Curcumina/química , Vírus da Dengue/imunologia , Composição de Medicamentos , Emulsões , Humanos , Nanopartículas , Tamanho da Partícula , Sorogrupo , Replicação Viral/efeitos dos fármacos
19.
Pharm Nanotechnol ; 7(4): 304-313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595848

RESUMO

BACKGROUND: Folic acid is essential in many metabolic processes and DNA synthesis. Nevertheless, folic acid is not stable, pH-sensitive, and deteriorated upon light exposure. OBJECTIVE: This work was aimed to improve folic acid stability within vitamin E-based nanoemulsion. METHODS: The nanoemulsion was prepared with self-nanoemulsification method by mixing vitamin E oil, Tween 20, and PEG 400. A pseudoternary phase diagram was constructed with aqueous titration to determine the optimum ratio for the mixture. The globule size, pH and entrapment efficiency were included in the nanoemulsion characterizations. In addition, the influence of centrifugation, storage, and pH on physical and chemical stabilities of folic acid nanoemulsion was evaluated. RESULTS: Optimum formula was obtained from vitamin E, Tween 20, and PEG 400 with the ratio of 1:11:1, and the folic acid amount was 8 mg. The size of folic acidloaded oil globule was 15.10 ± 1.51 nm, and the nanoemulsion pH was 6.24 ± 0.01. The nanoemulsion system was able to load the folic acid completely. Folic acid in nanoemulsion was stable after 14 days at room temperature, and it was more stable compared to folic acid in solution. In addition, the physical and chemical characteristics of folic acid in nanoemulsion was not affected by the simulated gastric condition. CONCLUSION: Hence, nanoemulsion is a promising strategy to enhance folic acid stability.


Assuntos
Emulsões/química , Ácido Fólico/química , Nanopartículas/química , Vitamina E/química , Administração Oral , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Polietilenoglicóis/química , Polissorbatos/química , Vitamina E/administração & dosagem
20.
Biochem Biophys Res Commun ; 519(4): 773-776, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31547987

RESUMO

Agaricus bisporus mannose binding protein (Abmb) demonstrates permeability to epithelial monolayer barrier of the intestine, resistance to gastrointestinal tract conditions and to proteolysis therefore it holds potential as a drug carrier for oral route administration. Abmb also display antiproliferative activity to breast cancer cells and stimulation of immune system thus could potentially be also developed for therapeutic purpose. It is not immunogenic or toxic thereby safe for use. In this paper we further provide evidence that Abmb also lacks of agglutinating activity despite sharing high structural homology to lectins. Abmb is thereby the only mannose specific binding protein that is not member of lectin family. This evidence provides further support on the use of Abmb as pharmaceutical or medicinal agent. Its molecular globularity that may contribute to its lack of agglutination capacity was also evaluated.


Assuntos
Agaricus/metabolismo , Proteínas Fúngicas/farmacologia , Lectinas/farmacologia , Lectina de Ligação a Manose/farmacologia , Animais , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Proteínas Fúngicas/administração & dosagem , Proteínas Fúngicas/química , Hemaglutinação/efeitos dos fármacos , Hemaglutinação/imunologia , Testes de Hemaglutinação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lectinas/administração & dosagem , Lectinas/química , Lectina de Ligação a Manose/administração & dosagem , Lectina de Ligação a Manose/química , Modelos Moleculares , Conformação Proteica
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