In Vitro α-Glucosidase and α-Amylase Inhibitory Activities of Free and Bound Phenolic Extracts from the Bran and Kernel Fractions of Five Sorghum Grain Genotypes

Diabetes is a global health challenge. Currently, an effective treatment for diabetes is to reduce the postprandial hyperglycaemia by inhibiting the carbohydrate hydrolysing enzymes in the digestive system. In this study, we investigated the in vitro α-glucosidase and α-amylase inhibitory effects of free and bound phenolic extracts, from the bran and kernel fractions of five sorghum grain genotypes. The results showed that the inhibitory effect of sorghum phenolic extracts depended on the phenolic concentration and composition. Sorghum with higher phenolic contents generally had higher inhibitory activity. Among the tested extracts, the brown sorghum (IS131C)-bran-free extract (BR-bran-free, half-maximal inhibitory concentration (IC50) = 18 ± 11 mg sorghum/mL) showed the strongest inhibition against α-glucosidase which was comparable to that of acarbose (IC50 = 1.39 ± 0.23 mg acarbose/mL). The red sorghum (Mr-Buster)-kernel-bound extract (RM-kernel-bound, IC50 = 160 ± 12 mg sorghum/mL) was the most potent in inhibiting α-amylase but was much weaker compared to acarbose (IC50 = 0.50 ± 0.03 mg acarbose/mL).

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In vitro Antioxidant, α-amylase and Horseradish Peroxidase Inhibitory Potential of Phenolics Extracts from Chamomilla pubescens, Pulicaria crispa and Rhanterium adpressum growing in Algeria

Current Enzyme Inhibition ◽

10.2174/1573408017666210506154339 ◽

2021 ◽

Vol 17 ◽

Author(s):

Feriel Mahfoudi ◽

Mahfoudi Reguia ◽

Mohamed Harrat ◽

Amar Djeridane ◽

Mohamed Yousfi

Keyword(s):

Antioxidant Activity ◽

Horseradish Peroxidase ◽

Ethyl Acetate ◽

Dry Matter ◽

Total Phenolic ◽

Inhibitory Effects ◽

Phenolic Contents ◽

Study Results ◽

Phenolic Extracts

Background: Plants are a main source of drugs for the therapy of a large number of diseases. Objective: The aim of the present work is to evaluate the in vitro antioxidant and anti-α-amylase and anti-peroxidases (HPR) potentials of phenolic extracts obtained from three spontaneous plants; growing in the South of Algeria such as (Chamomilla pubescens, Pulicaria crispa, and Rhanterium adpressum). This is the first report on the study of α-amylase and horseradish peroxidase (HRP) inhibitory activity for phenolic extracts from the Chamomilla pubescens and Pulicaria crispa plants. Method: The antioxidant activity was evaluated in vitro using four tests: DPPH, CUPRAC, FRAP, and ABTS. The phenolic, flavonoid, and tannin compounds of the three selected Algerian plants were quantified. Also, the inhibition of α-amylase and HRP was evaluated. Results: The quantification of the total phenolic contents revealed that they are widely variable, and depending on extraction solvents, the highest content was recorded by the ethyl acetate extract of Chamomilla pubescens (flowers) 774.93±60.14mg/100 g of dry matter. In all the antioxidant tests, ethyl acetate extracts showed the most effective activity, which the best was (VCEAC = 65.62 ±0.50 µM/g dry matter) of Pulicaria crispa for the DPPH test. Furthermore, the results of α-amylase and peroxidase inhibitory effects indicated that all plants extracts have inhibitory effects on the two enzymes, with AEIC values ranged from 76.55±3.54 to 149.54±6.68 μM/g of dry matter for the α-amylase, and CEIC values ranged from 8.89±2.22 to 9668.31±254.42 μM/g of dry matter for the peroxidase (HRP). Conclusion: The present study results suggest that the three Algerian spontaneous plant species (Rhanterium adpressum, Pulicaria crispa, and Chamomilla pubescens) inhibit peroxidase and α-amylase and exhibit a high antioxidant activity what can be related to the treatment of diabetes and thyroid diseases.

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In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646570 ◽

1989 ◽

Vol 61 (02) ◽

pp. 254-258 ◽

Cited By ~ 21

Author(s):

Margaret L Rand ◽

Peter L Gross ◽

Donna M Jakowec ◽

Marian A Packham ◽

J Fraser Mustard

Keyword(s):

Cyclic Amp ◽

Inhibitory Effect ◽

Rabbit Platelet ◽

Inhibitory Effects ◽

Low Concentrations ◽

Rabbit Platelets ◽

High Concentrations ◽

In Vitro Effects ◽

Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

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Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

Communications Biology ◽

10.1038/s42003-020-01577-x ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Vicky Mody ◽

Joanna Ho ◽

Savannah Wills ◽

Ahmed Mawri ◽

Latasha Lawson ◽

...

Keyword(s):

Inhibitory Effect ◽

Dynamics Simulation ◽

Simulation Studies ◽

Inhibitory Effects ◽

Major Threat ◽

Main Protease ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Computational Molecular Modeling

AbstractEmerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

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In Vitro Effects of Doxycycline on Replication of Feline Coronavirus

Pathogens ◽

10.3390/pathogens10030312 ◽

2021 ◽

Vol 10 (3) ◽

pp. 312

Author(s):

Magdalena Dunowska ◽

Sayani Ghosh

Keyword(s):

Inhibitory Concentration ◽

Infectious Virus ◽

Treatment Options ◽

Inhibitory Effect ◽

Virus Titration ◽

Reverse Transcription Quantitative Pcr ◽

In Vitro Effects ◽

Dose Dependent ◽

Feline Coronavirus

Feline infectious peritonitis (FIP) is a sporadic fatal disease of cats caused by a virulent variant of feline coronavirus (FCoV), referred to as FIP virus (FIPV). Treatment options are limited, and most of the affected cats die or are euthanized. Anecdotally, doxycycline has been used to treat FIP-affected cats, but there are currently no data to support or discourage such treatment. The aim of this study was to establish whether doxycycline inhibits replication of FIPV in vitro. The virus was cultured in Crandell-Rees feline kidney cells with various concentrations of doxycycline (0 to 50 µg/mL). The level of FIPV in cultures was determined by virus titration and FCoV-specific reverse-transcription quantitative PCR. Cell viability was also monitored. There was no difference in the level of infectious virus or viral RNA between doxycycline-treated and untreated cultures at 3, 12- and 18-hours post-infection. However, at 24 h, the growth of FIPV was inhibited by approximately two logs in cultures with >10 µg/mL doxycycline. This inhibition was dose-dependent, with inhibitory concentration 50% (IC50) 4.1 µg/mL and IC90 5.4 µg/mL. Our data suggest that doxycycline has some inhibitory effect on FIPV replication in vitro, which supports future clinical trials of its use for the treatment of FIP-affected cats.

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Amphetamine-Decreased Progesterone and Estradiol Release in Rat Granulosa Cells: The Regulatory Role of cAMP- and Ca2+-Mediated Signaling Pathways

Biomedicines ◽

10.3390/biomedicines9050493 ◽

2021 ◽

Vol 9 (5) ◽

pp. 493

Author(s):

Chung-Yu Chen ◽

Chien-Rung Chen ◽

Chiao-Nan Chen ◽

Paulus S. Wang ◽

Toby Mündel ◽

...

Keyword(s):

Granulosa Cells ◽

Prostaglandin F2α ◽

Inhibitory Effect ◽

Inhibitory Effects ◽

Steroidogenic Enzyme ◽

Estradiol Secretion ◽

Basal Release ◽

Ca2 Channels

The purpose of this study is to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells and the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells were cultured with various test drugs in the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level were measured. Additionally, the cytosolic-free Ca2+ concentrations ([Ca2+]i) were measured to examine the role of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited both basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 significantly decreased progesterone and estradiol basal release but failed to enhance a further amphetamine inhibitory effect. Amphetamine was capable of further suppressing the release of estradiol release under the presence of nifedipine. Pretreatment with the amphetamine for 2 h decreased the basal [Ca2+]i and prostaglandin F2α-stimulated increase of [Ca2+]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells through a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our current findings show that it is necessary to study the possibility of amphetamine perturbing reproduction in females.

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A STUDY OF THE INHIBITORY EFFECTS OF CHICK WHOLE EYE EXTRACT ON THE DEVELOPMENT OF THE LENS OF THE CHICK EMBRYO IN VITRO

Canadian Journal of Zoology ◽

10.1139/z66-065 ◽

1966 ◽

Vol 44 (4) ◽

pp. 661-676 ◽

Cited By ~ 1

Author(s):

Robert P. Thompson

Keyword(s):

Chick Embryo ◽

Nutrient Medium ◽

Inhibitory Effect ◽

Reactive System ◽

Vesicle Formation ◽

Inhibitory Effects ◽

Muscle Extract ◽

Lens Vesicle ◽

And Control

To demonstrate the phenomenon of homologous inhibition by clearly interpretable results in a readily reactive system, experiments were carried out to study the effect of chick whole eye extract on the development of the vesicular lens of the chick embryo in vitro. The heads of embryos of 11 through 13 somites were explanted onto nutrient medium diluted with varying amounts of the extract, and cultured for 30 hours. A total of 35 embryos exposed to concentrations of 1:1, 1:2, and 1:4 (extract to medium) showed complete inhibition of lens vesicle formation. Of a total of 53 embryos on concentrations of 1:8, 1:16, 1:32, and 1:64, more than 50% showed inhibition of vesicle formation. The inhibitory effect disappeared at a concentration of 1:128. Control material exposed to some equivalent concentrations of nutrient medium – saline mixtures showed inhibition of vesicle formation in only 15% of 33 embryos. Of a total of 27 control embryos exposed to ventricular muscle extract, approximately one-third showed inhibition of vesicle formation at concentrations of 1:8 and 1:16, with the inhibitory effect disappearing at 1:32. The implications of this result are discussed. Other factors and control experiments are described and their value is assessed.

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Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro.

Acta Biochimica Polonica ◽

10.18388/abp.2000_4068 ◽

2000 ◽

Vol 47 (1) ◽

pp. 113-120 ◽

Cited By ~ 3

Author(s):

K Bielawski ◽

A Galicka ◽

A Bielawska ◽

K Sredzińska

Keyword(s):

Protein Biosynthesis ◽

Elongation Factor ◽

Inhibitory Effect ◽

New Drugs ◽

Clinical Use ◽

Inhibitory Effects ◽

Inhibit Protein Synthesis ◽

Primary Target ◽

Eukaryotic Elongation Factor

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds differed in the precise mode of action. The inhibitory effect of I on the activity of the eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the binding site of eEF-2 on the ribosome was blocked by this compound. eEF-2 has been identified as the primary target of II and eEF-1 as the primary target of DAPI in the system studied.

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Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

Biomedicine Hub ◽

10.1159/000519564 ◽

2021 ◽

pp. 122-137

Author(s):

Chingju Lin ◽

Fuu-Jen Tsai ◽

Yuan-Man Hsu ◽

Tsung-Jung Ho ◽

Guo-Kai Wang ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Pathway Analysis ◽

Acute Inflammation ◽

Inhibitory Effect ◽

Pharmacological Effects ◽

Inhibitory Effects ◽

Rna Dependent Rna Polymerase ◽

Negative Impacts

Negative impacts of COVID-19 on human health and economic and social activities urge scientists to develop effective treatments. Baicalin is a natural flavonoid, extracted from a traditional medicinal plant, previously reported with anti-inflammatory activity. In this study, we used pharmacophore fitting and molecular docking to screen and determine docking patterns and the binding affinity of baicalin on 3 major targets of SARS-CoV-2 (3-chymotrypsin-like cysteine protease [3CLpro], papain-like protease [PLpro], and RNA-dependent RNA polymerase). The obtained data revealed that baicalin has high pharmacophore fitting on 3CLpro and predicted good binding affinity on PLpro. Moreover, using the enzymatic assay, we examined the inhibitory effect of baicalin in vitro on the screened enzymes. Baicalin also exhibits inhibitory effect on these proteases in vitro. Additionally, we performed pharmacophore-based screening of baicalin on human targets and conducted pathway analysis to explore the potential cytoprotective effects of baicalin in the host cell that may be beneficial for COVID-19 treatment. The result suggested that baicalin has multiple targets in human cell that may induce multiple pharmacological effects. The result of pathway analysis implied that these targets may be associated with baicalin-induced bioactivities that are involved with signals of pro-inflammation factors, such as cytokine and chemokine. Taken together with supportive data from the literature, the bioactivities of bailalin may be beneficial for COVID-19 treatment by reducing cytokine-induced acute inflammation. In conclusion, baicalin is potentially a good candidate for developing new therapeutic to treat COVID-19.

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Nisin and ε-poly-L-lysine as natural antimicrobials towards spoilage-associated Lactobacillus plantarum

Ciência Rural ◽

10.1590/0103-8478cr20200423 ◽

2021 ◽

Vol 51 (2) ◽

Author(s):

Fernanda Cristina Kandalski Bortolotto ◽

Maria Helena da Rosa Farfan ◽

Nathalia Cristina Kleinke Jede ◽

Gabriela Maia Danielski ◽

Renata Ernlund Freitas de Macedo

Keyword(s):

Lactic Acid ◽

Lactic Acid Bacteria ◽

Inhibitory Concentration ◽

Inhibitory Effect ◽

Minimal Bactericidal Concentration ◽

Natural Antimicrobials ◽

Food Preservatives ◽

Spoilage Bacteria ◽

Mass Spectrometry Identification

ABSTRACT: Sausages are highly susceptible to microbial spoilage. Lactic acid bacteria (LAB) is the main group of spoilage bacteria in vacuum packed cooked sausages. To control microbial growth natural antimicrobials have been used as food preservatives. The aim of this study was to identify strains of lactic acid bacteria isolated from spoiled commercial Calabresa sausages and use them in an in vitro challenge with the natural antimicrobials, nisin (NI) and ε-poly-L-lysine (ε-PL). Mass spectrometry identification of LAB isolated from sausages using MALDI-TOF revealed a predominance of L. plantarum in the LAB population. RAPD-PCR of L. plantarum strains showed four different genetic profiles. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of NI and ε-PL, alone and in combination, against a pool of different profiles L. plantarum were determined. MIC of NI and ε-PL were 0.468 mg/ L and 75 mg/ L; respectively, whereas MBC of NI and ε-PL were 12.48 mg/L and 150 mg/L, respectively. The combined effect of NI and ε-PL was determined using concentrations at 1/4 and 1/8 of individual MICs. Synergistic effect was confirmed at both concentrations showing a fractional inhibitory concentration index of 0.5 and 0.2, respectively. The combination of NI and ε-PL at a small concentration of 0.05 mg/L and 9.375 mg/L, respectively, showed inhibitory effect towards spoilage L. plantarum Results show the potential of the combined use of NI and ε-PL to control sausage spoilage-associated with lactobacilli.

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In vitro inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2020-0182 ◽

2021 ◽

Vol 36 (4) ◽

pp. 259-270

Author(s):

Boon Hooi Tan ◽

Nafees Ahemad ◽

Yan Pan ◽

Uma Devi Palanisamy ◽

Iekhsan Othman ◽

...

Keyword(s):

Cytochrome P450 ◽

High Performance ◽

Inhibitory Effect ◽

Inhibitory Effects ◽

Time Curve ◽

Clinical Drugs ◽

Inhibition Potencies ◽

P450 2D6

Abstract Objectives Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug–natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6. Methods CYP2D6 was heterologously expressed in Escherichia coli. CYP2D6–antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking. Results The high-performance liquid chromatography (HPLC)-based dextromethorphan O-demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC50 values >300 µM). Diacerein exhibited moderate inhibition with IC50 and K i values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC50=26.22 μM and K i =32.27 μM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro–in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition. Conclusions Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

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