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1.
Protein Pept Lett ; 30(11): 913-929, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38008946

RESUMO

This review describes the specific features of families of Conus venom peptides (conotoxins or conopeptides) that represent twelve pharmacological classes. Members of these conopeptide families are targeted to voltage-gated ion channels, such as calcium, sodium, and potassium channels. The conopeptides covered in this work include omega-conotoxins and contryphans with calcium channels as targets; mu-conotoxins, muO-conotoxins, muP-conotoxins, delta-conotoxins and iota-conotoxin with sodium channels as targets; and kappa-conotoxins, kappaM-conotoxins, kappaO-conotoxin, conkunitzins, and conorfamide with potassium channels as targets. The review covers the peptides that have been characterized over the last two decades with respect to their physiological targets and/or potential pharmacological applications, or those that have been discovered earlier but with noteworthy features elucidated in more recent studies. Some of these peptides have the potential to be developed as therapies for nerve, muscle, and heart conditions associated with dysfunctions in voltage-gated ion channels. The gating process of an ion channel subtype in neurons triggers various biological activities, including regulation of gene expression, contraction, neurotransmitter secretion, and transmission of electrical impulses. Studies on conopeptides and their interactions with calcium, sodium, and potassium channels provide evidence for Conus peptides as neuroscience research probes and therapeutic leads.


Assuntos
Conotoxinas , Caramujo Conus , Animais , Caramujo Conus/metabolismo , Cálcio/metabolismo , Canais de Potássio/metabolismo , Sódio/metabolismo , Conotoxinas/farmacologia , Conotoxinas/química , Peptídeos/química
2.
Cell Rep ; 42(8): 112858, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37494189

RESUMO

The sodium-activated Slo2.2 channel is abundantly expressed in the brain, playing a critical role in regulating neuronal excitability. The Na+-binding site and the underlying mechanisms of Na+-dependent activation remain unclear. Here, we present cryoelectron microscopy (cryo-EM) structures of human Slo2.2 in closed, open, and inhibitor-bound form at resolutions of 2.6-3.2 Å, revealing gating mechanisms of Slo2.2 regulation by cations and a potent inhibitor. The cytoplasmic gating ring domain of the closed Slo2.2 harbors multiple K+ and Zn2+ sites, which stabilize the channel in the closed conformation. The open Slo2.2 structure reveals at least two Na+-sensitive sites where Na+ binding induces expansion and rotation of the gating ring that opens the inner gate. Furthermore, a potent inhibitor wedges into a pocket formed by pore helix and S6 helix and blocks the pore. Together, our results provide a comprehensive structural framework for the investigation of Slo2.2 channel gating, Na+ sensation, and inhibition.


Assuntos
Canais de Potássio , Sódio , Humanos , Canais de Potássio/metabolismo , Microscopia Crioeletrônica , Canais de Potássio Ativados por Sódio , Sódio/metabolismo
3.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446101

RESUMO

A five-year-old girl presented with headache attacks, clumsiness, and a history of transient gait disturbances. She and her father, mother, twin sister, and brother underwent neurological evaluation, neuroimaging, and exome sequencing covering 357 genes associated with movement disorders. Sequencing revealed the new variant KCND3 c.838G>A, p.E280K in the father and sisters, but not in the mother and brother. KCND3 encodes voltage-gated potassium channel D3 (Kv4.3) and mutations have been associated with spinocerebellar ataxia type 19/22 (SCA19/22) and cardiac arrhythmias. SCA19/22 is characterized by ataxia, Parkinsonism, peripheral neuropathy, and sometimes, intellectual disability. Neuroimaging, EEG, and ECG were unremarkable. Mild developmental delay with impaired fluid reasoning was observed in both sisters, but not in the brother. None of the family members demonstrated ataxia or parkinsonism. In Xenopus oocyte electrophysiology experiments, E280K was associated with a rightward shift in the Kv4.3 voltage-activation relationship of 11 mV for WT/E280K and +17 mV for E280K/E280K relative to WT/WT. Steady-state inactivation was similarly right-shifted. Maximal peak current amplitudes were similar for WT/WT, WT/E280K, and E280K/E280K. Our data indicate that Kv4.3 E280K affects channel activation and inactivation and is associated with developmental delay. However, E280K appears to be relatively benign considering it does not result in overt ataxia.


Assuntos
Ataxia Cerebelar , Degenerações Espinocerebelares , Masculino , Feminino , Humanos , Degenerações Espinocerebelares/genética , Canais de Potássio Shal/genética , Mutação de Sentido Incorreto , Mutação , Ataxia
5.
Diabetes Metab Syndr Obes ; 15: 1771-1784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711690

RESUMO

Purpose: Differences in metformin effect on glycemic control in type 2 Diabetes (T2D) have been associated with diet, obesity, years since T2D diagnosis and genetic factors, such as the Met408Val (rs628031) SLC22A1/OCT1 gene polymorphism. This study aimed to analyze the effect of metformin and diet on glycemic control and its association with the Met408Val polymorphism in patients with T2D from western Mexico. Patients and Methods: A total of 240 T2D adult patients were enrolled in this cross-sectional study. Anti-hyperglycemic therapy, dietary intake, body composition and glycemic profile were recorded and the determination of genotypes of SLC22A1/OCT1 gene (rs628031) was performed using an allelic discrimination assay. Results: The type of metformin therapy was 47% monotherapy, 45% dual therapy (metformin+glibenclamide or metformin+insulin) and 8% triple therapy (metformin+glibenclamide+insulin). Individuals with metformin monotherapy had a higher glycemic control frequency (%HbA1c <7.0) compared with the dual and triple treatment schemes (77% vs 35% and 15%, respectively; p<0.001). Interestingly, a high potassium intake was documented in the three anti-hyperglycemic therapies and a lower intake of micronutrients, including calcium, magnesium, and zinc. An interaction was found between calcium intake and carriers of the risk allele A (408Val) with %HbA1c (P interaction=0.028), and potassium intake with the TyG index (P interaction=0.027). In addition, there was a positive correlation between calcium intake and %HbA1c (r=0.682; p=0.010), and potassium intake vs TyG index (r=0.593; p=0.033) in risk allele A (408Val) carriers with metformin monotherapy. Genotype frequencies were GG homozygotes (76.6%), GA heterozygotes (21.5%) and AA homozygotes (1.9%). The allele frequency was 87.4% for the ancestral allele G and 12.6% for the risk allele A. Conclusion: These findings suggest a differing effect of metformin on glycemic control regarding calcium and potassium intake and the Met408Val SLC22A1/OCT1 gene polymorphism in T2D patients.

6.
Carbohydr Polym ; 260: 117778, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712134

RESUMO

To deal with serious environmental damage resulting from plastic packaging materials, biodegradable films using natural products have gained considerable attention. Here, we provide a simple, fast, and environmentally-friendly route to construct a biodegradable film using chitosan (CS), bacterial cellulose (BC), and curcumin (Cur). Composite films (CSn-BC-Cur) using CS with different molecular weights were investigated, and their water moisture content (MC), water solubility (WS), contact angle (CA), mechanical properties, barrier properties, and antioxidant properties were compared. The obtained films were characterized by SEM, XRD, and TGA. The results showed that chitosan with a higher molecular weight presented higher contact angles and mechanical properties, along with a lower moisture content, water vapor transmission rate, and oxygen transmission rate. Furthermore, when the composite film was placed in 95 % ethanol, it released active substances. The results suggest that these composite films can be used as promising materials for food packaging.


Assuntos
Celulose/química , Quitosana/química , Curcumina/química , Embalagem de Alimentos , Antioxidantes/química , Resistência ao Cisalhamento , Solubilidade , Temperatura , Água/química
7.
Food Chem ; 347: 129084, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33486366

RESUMO

Milk proteins and polyphenols are increasingly being studied as functional ingredients due to the epidemiologically-proved health benefits. In this study, composite ß-lactoglobulin (ß-lg) or ß-lactoglobulin nanoparticles (ß-lgNPs)-3,5-di-O-caffeoylquinic acid (3,5diCQA) with superior physicochemical and antioxidant activity (AA) were produced using ß-lg and 3,5-di-O-caffeoylquinic acid. The main interactions between ß-lg or ß-lgNPs with 3,5diCQA were hydrogen bonding and hydrophobic effects. The 3,5diCQA caused a decrease in α-helix and ß-sheet structure with a corresponding increase in unordered structure. Compared to ß-lg alone, composite ß-lg or ß-lgNPs-3,5diCQA slightly decreased the particle size but increased their negative surface potentials especially for ß-lg or ß-lgNPs at a molar ratio of 5:1. The addition of 3,5diCQA appreciably improved the AA in a dose-dependent manner. These results shed light on the structural, physicochemical, and AA of composite ß-lg or ß-lgNPs-3,5diCQA non-covalent complexes, important for application as functional ingredients in food solutions as well as in the pharmaceutical industry.


Assuntos
Antioxidantes/química , Ácido Clorogênico/análogos & derivados , Lactoglobulinas/química , Nanopartículas/química , Animais , Ácido Clorogênico/química , Ácido Clorogênico/metabolismo , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Lactoglobulinas/metabolismo , Tamanho da Partícula , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta
8.
Food Chem ; 340: 127950, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896780

RESUMO

This study aimed to prepare anthocyanin-rich microcapsules by spray and freeze-drying complex coacervated double emulsion using gelatin-acacia gum (GE-AG) and chitosan-carboxymethylcellulose (CS-CMC) and to investigate their properties and in vitro release kinetics. Microencapsulation efficiency (MEE) of the microcapsules varied from 84.9% to 94.7%. CS-CMS microcapsules showed significantly higher MEEs than those of GE-AG microcapsules. A significant higher MEE and lower moisture content and hygroscopicity was observed in spray-dried double emulsion (SDE) microcapsules. Freeze-dried double emulsion (FDE) microcapsules possessed higher total anthocyanin and total phenolic contents. The best fit for release kinetics was achieved using first-order and Higuchi models for SDE and FDE microcapsules, respectively. Diffusion-controlled release in the simulated gastric fluid was found for SDE microcapsules, while erosion-controlled release in simulated gastric and intestinal fluids predominated for FDE microcapsules. These findings suggest that the microcapsules can be applied for loading anthocyanins as a nutraceutical with controllable release requirement.


Assuntos
Antocianinas/química , Cápsulas , Carboximetilcelulose Sódica/química , Quitosana/química , Liberação Controlada de Fármacos , Emulsões , Liofilização , Goma Arábica/química , Cinética , Fenóis/química
9.
Food Chem ; 336: 127669, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32758804

RESUMO

Curcumin was recently attracted great interest owing to its multiple bioactivities; however, the use of curcumin was hindered by its poor solubility and stability. In this study, curcumin-nisin-soy soluble polysaccharide nanoparticles (Cur-Nisin-SSPS-NPs, size = 118.76 nm) have been successfully elaborated to improve the application of curcumin. The formation of Cur-Nisin-SSPS-NPs was mediated by amphiphilic and positively charged nisin: SSPS encapsulated nisin, which was mainly driven by electrostatic attraction. And nisin-SSPS complex encapsulated curcumin mainly through hydrophobic interactions between nisin and curcumin. The encapsulation efficiency of curcumin (91.66%) in this novel nanocarriers was significantly higher than that in nanoparticles prepared by a single SSPS (31.82%) or nisin (41.69%), most likely because more hydrophobic regions of nisin were exposed after interacting with SSPS through electrostatic interaction. Consequently, this facile and green nanocarriers improved the solubility/dispersibility and stability of curcumin and nisin, as well as endowed SSPS-based nanoparticles with antioxidant and antimicrobial activities.


Assuntos
Curcumina/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Nisina/química , Polissacarídeos/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Curcumina/química , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Imidazóis , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Morfolinas , Solubilidade , Espectrofotometria Ultravioleta
10.
Regen Ther ; 14: 11-18, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31970268

RESUMO

INTRODUCTION: Inflammatory response plays an important role in the disease progress or therapeutic effect. In this context, it is highly required to develop a technology to visualize the inflammatory response. In this study, macrophages and their microRNA (miRNA) which are involved in the inflammatory response, were focused while a system of molecular beacon (MB) to detect the miRNA of macrophages was designed and prepared. METHODS: Gelatin nanospheres were prepared by the conventional coacervation method. An antibody with an affinity for the surface receptor of macrophages was immobilized onto the gelatin nanospheres by several methods. A nucleic acid-based MB for a pro-inflammatory miRNA 155-5p was designed and incorporated into the antibody-immobilized gelatin nanospheres (MB-gelatin NS). Macrophages before and after the polarization into pro-inflammatory or anti-inflammatory phenotypes were cultured with the MB-gelatin NS and change in the intracellular fluorescence was observed. RESULTS: The antibody-immobilized gelatin nanospheres prepared by a coupling between the amino groups of gelatin and the sugar chains of antibody with NaIO4 showed the highest affinity for cellular receptor. MB complexed with the cell-penetrating (CP) peptide was successfully incorporated into the antibody-immobilized gelatin nanospheres. When cultured with pro-inflammatory macrophages, MB-gelatin NS efficiently detected the miRNA 155-5p to emit fluorescence. CONCLUSIONS: By the NaIO4 method, the antibody was immobilized onto gelatin nanospheres with a high affinity remaining while the MB was incorporated into the antibody-immobilized gelatin nanospheres. The MB incorporated allowed mRNA to visualize the pro-inflammatory nature of macrophages.

11.
Carbohydr Polym ; 231: 115729, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888843

RESUMO

This paper reports the preparation, characterization and properties of synthetic melanin-like nanoparticle (MNP) reinforced chitosan nanocomposite films. The MNP was prepared using dopamine hydrochloride and sodium hydroxide which followed by spontaneous oxidation. The prepared MNP was spherical in shape and in the size range of ∼100 nm. The MNP was used as a functional nanofiller to produce the chitosan/MNP nanocomposite films using simple solution mixing and casting method. The MNP are evenly dispersed and biocompatible with chitosan to form the nanocomposite films. The incorporation of MNP enhances the ultraviolet blocking, mechanical properties, swelling ratio, and hydrophobicity of the nanocomposite films. The reinforcement of MNP in chitosan does not deteriorate the thermal stability and water vapor barrier property of the nanocomposite films. Furthermore, the prepared nanocomposite films show strong antioxidant activity. The developed chitosan/MNP nanocomposite films can applied to active food packaging and biomedical packaging.

12.
Annu Rev Pharmacol Toxicol ; 60: 219-240, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31337271

RESUMO

The three small-conductance calcium-activated potassium (KCa2) channels and the related intermediate-conductance KCa3.1 channel are voltage-independent K+ channels that mediate calcium-induced membrane hyperpolarization. When intracellular calcium increases in the channel vicinity, it calcifies the flexible N lobe of the channel-bound calmodulin, which then swings over to the S4-S5 linker and opens the channel. KCa2 and KCa3.1 channels are highly druggable and offer multiple binding sites for venom peptides and small-molecule blockers as well as for positive- and negative-gating modulators. In this review, we briefly summarize the physiological role of KCa channels and then discuss the pharmacophores and the mechanism of action of the most commonly used peptidic and small-molecule KCa2 and KCa3.1 modulators. Finally, we describe the progress that has been made in advancing KCa3.1 blockers and KCa2.2 negative- and positive-gating modulators toward the clinic for neurological and cardiovascular diseases and discuss the remaining challenges.


Assuntos
Canais de Potássio Ativados por Cálcio de Condutância Intermediária/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Baixa/efeitos dos fármacos , Animais , Sítios de Ligação , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo
13.
Front Pharmacol ; 10: 972, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616290

RESUMO

Calcium-activated K+ channels constitute attractive targets for the treatment of neurological and cardiovascular diseases. To explain why certain 2-aminobenzothiazole/oxazole-type KCa activators (SKAs) are KCa3.1 selective we previously generated homology models of the C-terminal calmodulin-binding domain (CaM-BD) of KCa3.1 and KCa2.3 in complex with CaM using Rosetta modeling software. We here attempted to employ this atomistic level understanding of KCa activator binding to switch selectivity around and design KCa2.2 selective activators as potential anticonvulsants. In this structure-based drug design approach we used RosettaLigand docking and carefully compared the binding poses of various SKA compounds in the KCa2.2 and KCa3.1 CaM-BD/CaM interface pocket. Based on differences between residues in the KCa2.2 and KCa.3.1 models we virtually designed 168 new SKA compounds. The compounds that were predicted to be both potent and KCa2.2 selective were synthesized, and their activity and selectivity tested by manual or automated electrophysiology. However, we failed to identify any KCa2.2 selective compounds. Based on the full-length KCa3.1 structure it was recently demonstrated that the C-terminal crystal dimer was an artefact and suggested that the "real" binding pocket for the KCa activators is located at the S4-S5 linker. We here confirmed this structural hypothesis through mutagenesis and now offer a new, corrected binding site model for the SKA-type KCa channel activators. SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine) is binding in the interface between the CaM N-lobe and the S4-S5 linker where it makes van der Waals contacts with S181 and L185 in the S45A helix of KCa3.1.

14.
Neurosci Lett ; 704: 159-163, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30965109

RESUMO

Background ADAM22 and ADAM23 are transmembrane proteins that bind the secreted synaptic protein LGI1 and associate with Kv1.1/Kv1.4 potassium channels. However, the roles of these proteins in regulated voltage-gated potassium currents are poorly understood. Methods Cultured cells were transfected to express ADAM22, ADAM23, and Kv1.1/Kv1.4. Voltage-gated potassium currents were measured by whole-cell patch-clamp. Immunostaining Kv1.1 with fluorescent antibodies and fluorescently tagged Kv1.1 subunits was used to measure the effects of ADAM proteins on cell-surface and total expression of Kv1.1 channels. LGI1-conditioned media was added to assess the effect on LGI1 on Kv1.1 currents. Results Cells transfected with Kv1.1/Kv1.4 showed voltage-gated potassium currents (Kv1.1 currents). ADAM23 was a powerful negative regulator of Kv1.1 currents and caused decreased surface expression of Kv1.1 subunits. This decrease in current was not mediated by clathrin-dependent endocytosis. LGI1-conditioned media did not affect the negative regulation of Kv1.1 currents by ADAM23. ADAM22 had no significant effect on Kv1.1 currents by itself, but in the presence of LGI1-conditioned media markedly potentiated Kv1.1 currents without changing channel activation kinetics. Conclusions ADAM22 and ADAM23 have opposite effects on Kv1.1 currents. The relative expression of these proteins, and the availability of LGI1 may shape the expression of Kv1.1 currents in different neuronal membrane domains.


Assuntos
Proteínas ADAM/metabolismo , Canal de Potássio Kv1.1/metabolismo , Canal de Potássio Kv1.4/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas ADAM/genética , Animais , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Canal de Potássio Kv1.1/genética , Canal de Potássio Kv1.4/genética , Camundongos , Proteínas do Tecido Nervoso/genética
15.
Neural Regen Res ; 14(5): 826-833, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30688268

RESUMO

Bisperoxo (1,10-phenanthroline) oxovanadate (BpV) can reportedly block the cell cycle. The present study examined whether BpV alters gene expression by affecting DNA methyltransferases (DNMTs), which would impact the cell cycle. Immortalized mouse hippocampal neuronal precursor cells (HT22) were treated with 0.3 or 3 µM BpV. Proliferation, morphology, and viability of HT22 cells were detected with an IncuCyte real-time video imaging system or inverted microscope and 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium, respectively. mRNA and protein expression of DNMTs and p21 in HT22 cells was detected by real-time polymerase chain reaction and immunoblotting, respectively. In addition, DNMT activity was measured with an enzyme-linked immunosorbent assay. Effects of BpV on the cell cycle were analyzed using flow cytometry. Results demonstrated that treatment with 0.3 µM BpV did not affect cell proliferation, morphology, or viability; however, treatment with 3 µM BpV decreased cell viability, increased expression of both DNMT3B mRNA and protein, and inhibited the proliferation of HT22 cells; and 3 µM BpV also blocked the cell cycle and increased expression of the regulatory factor p21 by increasing DNMT expression in mouse hippocampal neurons.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-857529

RESUMO

OBJECTIVE To explore whether different concentrations of potassium bisperoxo (1,10-phenanthroline) oxovanadate [BPV (phen)) affect cell cycle by regulating the expression of DNA meth-yltranferases (DNMT) and cell cycle-related genes. METHODS HT22 cells were treated with BPV (phen) 0.3 and 3 μ mol • L-1 for 24 h. The cell viability was detected by MTS assay, cell cycle was detected by flow cytometry, the activity of DNMT was detected by ELISA, the mRNA expressions of p21, DNMT1, DNMT3A and DNMT3B were measured with real-time quantitative PCR, while the levels of corresponding proteins were measured by Western blotting. RESULTS Compared with the DMSO control group, BPV(phen) 0.3 μ mol• L-1 did not affect cell viability, but the cell viability of BPV(phen) 3 pmol-L-1 increased signifi-cantly (P<0.05). There was no significant difference in cell cycle between DMSO control and BPV(phen) 0.3 nmol-L-1 group, but the proportion of cells in S phase increased((76.0±1.6)%)(P<0.05) and in G2 phase decreased ((2.1 ±1.5)%) (P<0.05) of BPV(phen) 3.0 μ mol • L-1 group. The intracellular DNMT activity of BPV(phen) 3.0 Mmol • L-1 group was significantly increased compared with the DMSO control group (F<0.05). There was no significant difference in the mRNA expressions of p21, DNMT1, DNMT3A and DNMT3B between DMSO control and BPV(phen) 0.3 μ mol • L-1 group, but all increased in BPV(phen) 3.0 μ mol • L-1 group (P<0.05, P<0.01). Western blotting results showed that there was no significant difference in the protein expressions of P21, DNMT1, DNMT3A and DNMT3B between DMSO control and BPV (phen) 0.3 μ mol • L-1 group, but only the protein expressions of DNMT3B and P21 of BPV (phen) 3.0 μ mol • L-1 group increased significantly (F<0.05). CONCLUSION BPV(phen) can regulate the expression of downstream and cell cycle-related genes by altering the expression of DNMTs, which in turn affects the growth and proliferation of HT22 cells.

17.
Food Chem ; 261: 260-266, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-29739592

RESUMO

Acidified water extraction of total anthocyanin content, total phenol content and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity from black soybeans (Glycine max [L.] Merr. Cheongja4ho) was optimized using response surface methodology (RSM). A five-level, three-factor central composite design was employed to optimize the conditions for the maximum yields of these three components using19 different experiments. The HCl concentration (0.3-0.5%), solid-liquid ratio (1/30-1/50 g/mL) and extraction temperature (30-50 °C) significantly affected three components. The optimized conditions were HCl concentration of 0.359%, solid-liquid ratio of 1/54.2 g/mL and extraction temperature of 56.8 °C for total anthocyanin content (136.68 mg/100 g), total phenol content (1197.09 mg/100 g) and ABTS+ scavenging activity (211.65 mg/100 g). These experimental values fit well with the predicted values. Among three anthocyanins found in the black soybean extracts, cyanidin-3-O-glucoside was the major one (65-73% of the total), followed by petunidin-3-O-glucoside (17-23%) and delphinidin-3-O-glucoside (10-12%).


Assuntos
Antocianinas/isolamento & purificação , Fracionamento Químico/métodos , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Água/química , Antocianinas/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Fenóis/química
18.
Food Chem ; 250: 148-154, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29412905

RESUMO

This study was conducted to investigate the effect of lactic acid bacteria (LAB) strains on color properties, phenolic profile and antioxidant activities of mulberry juice. Mulberry juice was separately fermented at 37 °C for 36 h using Lactobacillus plantarum, Lactobacillus acidophilus and Lactobacillus paracasei. The results showed that lactic acid fermentation impacted on the color of the juice. Moreover, the study demonstrated that LABs impacted on the phenolic profile of the juice. Syringic acid, cyanidin-3-O-rutinoside and quercetin were the predominant phenolic acid, anthocyanin and flavonol respectively in the lactic-acid-fermented mulberry juice. The degree of radical scavenging activity was species-specific with the L. plantarum fermented juice having the highest radical scavenging activities. The correlation analysis demonstrated that flavonols and anthocyanins were mostly responsible for the increased in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity while phenolic acids and flavonols were responsible for 2,2-diphenyl-1-picrylhydrazyl scavenging activity and reducing power capacity of the fermented juice.


Assuntos
Fermentação , Sucos de Frutas e Vegetais/microbiologia , Ácido Láctico/metabolismo , Lactobacillus/metabolismo , Morus/metabolismo , Morus/microbiologia , Fenóis/análise , Antioxidantes/análise , Antioxidantes/química , Cor , Morus/química , Fenóis/química
19.
Bioorg Med Chem ; 25(14): 3719-3735, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28522264

RESUMO

With the aim to discover a gastric antisecretory agent more potent than the existing proton pump inhibitors, novel 3,4-dihydro-1H-spiro(naphthalene-2,2'-piperidin)-1-one derivatives, which could occupy two important lipophilic pockets (described as LP-1 and LP-2) of H+,K+-ATPase and can strongly bind to the K+-binding site, were designed based on a docking model. Among the compounds synthesized, compound 4d showed a strong H+,K+-ATPase-inhibitory activity and a high stomach concentration in rats, resulting in potent inhibitory action on histamine-stimulated gastric acid secretion in rats. Furthermore, 4d exerted significant inhibitory action on histamine-stimulated gastric-acid secretion in rats with a rapid onset and moderate duration of action after the administration. These findings may lead to a new insight into the drug design of potassium-competitive acid blockers.


Assuntos
ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Piperidinas/química , Potássio/metabolismo , Inibidores da Bomba de Prótons/síntese química , Compostos de Espiro/química , Administração Intravenosa , Animais , Área Sob a Curva , Sítios de Ligação , Avaliação Pré-Clínica de Medicamentos , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/química , Meia-Vida , Histamina/toxicidade , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Naftalenos/química , Piperidinas/síntese química , Piperidinas/farmacocinética , Potássio/química , Inibidores da Bomba de Prótons/química , Inibidores da Bomba de Prótons/farmacocinética , Curva ROC , Ratos , Compostos de Espiro/síntese química , Compostos de Espiro/farmacocinética , Relação Estrutura-Atividade
20.
Int J Biol Macromol ; 97: 46-54, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28064055

RESUMO

Chinese angelica polysaccharides (CAP) and selenizing CAP (sCAP) were prepared and identified through FTIR and SEM observation. Their antioxidant activities in vitro and hepatoprotective effects in vivo were compared by free radical-scavenging tests or with CCl4-induced hepatic injury model mice. The results showed that for DPPH radical, superoxide anion and hydroxyl radical, the scavenging capabilities of sCAP were significantly stronger than those of CAP. In hepatic injury model mice, sCAP could significantly reduce ALT, AST and ALP contents and raised TP content in serum, significantly reduce MDA and ROS contents and raised SOD and T-AOC activities in liver homogenate in comparison with CAP; obviously relieve the pathological changes of liver and significantly inhibit the expressions of p-ERK, p-JNK and p-p38 protein as compared with those in model control group. These results indicate that selenylation modification can enhance the antioxidant and hepatoprotective actions of Chinese angelica polysaccharide. A action mechanism of sCAP is suppressing the protein expression of MAPK signaling pathway.


Assuntos
Angelica sinensis/química , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Selênio/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoproteção/efeitos dos fármacos , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
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