scholarly journals Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1215 ◽  
Author(s):  
Jayeong Hwang ◽  
Kumju Youn ◽  
Yeongseon Ji ◽  
Seonah Lee ◽  
Gyutae Lim ◽  
...  
Keyword(s):  
Docking Simulation ◽  
Inhibitory Effect ◽  
Potential Effect ◽  
Van Der Waals Interactions ◽  
Inhibitory Effects ◽  
Computational Docking ◽  
In Silico Docking ◽  
Ic50 Values ◽  
Physiological Benefits

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer’s disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase inhibitor, zerumbone, using in vitro target enzyme assays, as well as in silico docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) simulation. Zerumbone showed a predominant cholinesterase inhibitory property with IC50 values of 2.74 ± 0.48 µM and 4.12 ± 0.42 µM for AChE and BChE, respectively; however, the modes of inhibition were different. Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects. Furthermore, zerumbone showed the best physicochemical properties for both bioavailability and blood–brain barrier (BBB) permeability. Together, in the present study, zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB, suggesting a strong potential for its physiological benefits and/or pharmacological efficacy in the prevention of AD.

scholarly journals α-Glucosidase inhibitors: consistency of in silico docking data with in vitro inhibitory data and inhibitory effect prediction of quercetin derivatives

2019 ◽  
Vol 10 (10) ◽  
pp. 6312-6321 ◽  
Author(s):  
Jianzhong Zhu ◽  
Bin Zhang ◽  
Chinping Tan ◽  
Qiang Huang
Keyword(s):  
In Silico ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Quercetin Derivatives ◽  
In Silico Docking ◽  
Glucosidase Inhibitors ◽  
The Relationship

The relationship between in silico and in vitro experiments regarding the inhibitory effects of polyphenols on α-glucosidase was investigated.

scholarly journals Comparison of α-amylase, α-glucosidase and lipase inhibitory activity of different types of vinegar

Food Research ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 485-491
Author(s):  
F. Yasmin ◽  
K.N. Abdul Razak ◽  
N. Abdul Samad ◽  
T. Widyawati ◽  
N.A. Yusoff
Keyword(s):  
Enzyme Inhibition ◽  
Brown Rice ◽  
Inhibitory Effect ◽  
Glycaemic Index ◽  
Inhibitory Effects ◽  
Porcine Pancreas ◽  
Apple Cider ◽  
Ic50 Values ◽  
Diabetes And Obesity

Vinegar is regarded as a fine example of a traditional food that has several medicinal values. It is used as a home-remedy for the management of diabetes and obesity. We investigated how selected vinegar inhibit the digestive enzymes involved in carbohydrate and lipid metabolism. A total of seven types of vinegar were examined as follows: apple cider (ACV), balsamic (BV), brown rice (BRV), distilled white (DWV), malt (MV), nipah palm (NPV), and red wine (RWV) vinegar. In vitro enzyme inhibition tests were performed using α-amylase and lipase from porcine pancreas, and α-glucosidase from Saccharomyces cerevisiae. In the α-amylase assay, NPV (IC50 = 60.97±1.71 mg/mL) exhibited the strongest inhibitory effect, while RWV (IC50 =786.7±0.96 mg/mL) showed the lowest inhibitory effect. RWV (IC50 =92.49±1.51 mg/mL), by contrast, had the highest inhibitory effect against α-glucosidase and was followed by NPV (IC50 = 227.5±1.06 mg/ mL) and BRV (IC50 = 565.1±2.65 mg/mL). All of the samples showed potent inhibitory effects against pancreatic lipase, with MV having the strongest and ACV the lowest effects, respectively. IC50 values ranged from 48.45 mg/mL to 399.8 mg/mL. A concentration-dependent inhibitory effect was recorded for each of the vinegar against all three tested enzymes. None of the vinegar, however, exceeded the effects recorded for the standard drugs. Interestingly, a weak correlation was found between total acidity and enzyme inhibition, which asserted the presence of bioactive compounds in the vinegar. As a conclusion, vinegar can be incorporated into the diet to lower the meal’s glycaemic index and benefit those at risk of diabetes as well as diabetics.

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

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
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.

Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major

2020 ◽  
Vol 20 (4) ◽  
pp. 550-555 ◽  
Author(s):  
Lima Asgharpour Sarouey ◽  
Parvaneh Rahimi-Moghaddam ◽  
Fatemeh Tabatabaie ◽  
Khadijeh Khanaliha
Keyword(s):  
Flow Cytometry ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Inhibitory Effect ◽  
Control Group ◽  
Secondary Infections ◽  
Ic50 Values ◽  
J774 Cells ◽  
Mtt Assays

: As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. Methods: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 μg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. Results: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 μg/ml and 23.73 μg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 μg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Conclusion: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.

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

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.

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

Biomedicines ◽  
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.

scholarly journals Combined Ensemble Docking and Machine Learning in Identification of Therapeutic Agents with Potential Inhibitory Effect on Human CES1

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2747 ◽  
Author(s):  
Eliane Briand ◽  
Ragnar Thomsen ◽  
Kristian Linnet ◽  
Henrik Berg Rasmussen ◽  
Søren Brunak ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Interactions ◽  
Scoring Function ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Therapeutic Agents ◽  
Learning Approaches ◽  
Ensemble Docking ◽  
Ic50 Values

The human carboxylesterase 1 (CES1), responsible for the biotransformation of many diverse therapeutic agents, may contribute to the occurrence of adverse drug reactions and therapeutic failure through drug interactions. The present study is designed to address the issue of potential drug interactions resulting from the inhibition of CES1. Based on an ensemble of 10 crystal structures complexed with different ligands and a set of 294 known CES1 ligands, we used docking (Autodock Vina) and machine learning methodologies (LDA, QDA and multilayer perceptron), considering the different energy terms from the scoring function to assess the best combination to enable the identification of CES1 inhibitors. The protocol was then applied on a library of 1114 FDA-approved drugs and eight drugs were selected for in vitro CES1 inhibition. An inhibition effect was observed for diltiazem (IC50 = 13.9 µM). Three others drugs (benztropine, iloprost and treprostinil), exhibited a weak CES1 inhibitory effects with IC50 values of 298.2 µM, 366.8 µM and 391.6 µM respectively. In conclusion, the binding site of CES1 is relatively flexible and can adapt its conformation to different types of ligands. Combining ensemble docking and machine learning approaches improves the prediction of CES1 inhibitors compared to a docking study using only one crystal structure.

scholarly journals 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

Foods ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1301
Author(s):  
Yun Xiong ◽  
Ken Ng ◽  
Pangzhen Zhang ◽  
Robyn Dorothy Warner ◽  
Shuibao Shen ◽  
...  
Keyword(s):  
Digestive System ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Phenolic Contents ◽  
Inhibitory Activities ◽  
Sorghum Grain ◽  
Global Health Challenge ◽  
Phenolic Extracts

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).

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

1966 ◽  
Vol 44 (4) ◽  
pp. 661-676 ◽  
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.

Antifungal and allelopathic activities of sesquiterpenes from Solidago canadensis

2021 ◽  
Vol 25 ◽  
Author(s):  
Na Liu ◽  
Meina Song ◽  
Yulin Sun ◽  
Fengying Yang ◽  
Haina Yu ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Seed Germination ◽  
Invasive Plant ◽  
2D Nmr ◽  
Solidago Canadensis ◽  
Significant Activity ◽  
Inhibitory Effects ◽  
Ic50 Values ◽  
Allelopathic Effects

: One new eudesmane sesquiterpene (1) and one new chromolaevane sesquiterpene (2), along with 19 known compounds, have been isolated from the invasive plant Solidago canadensis. Their structures were established by spectroscopic means including 1D/2D-NMR and HR-ESIMS analyses. Compounds 10 and 12, in combination with fluconazole, showed significant activity in an in vitro synergistic antifungal assay against Candida albicans, with FIC values of <0.15625 and <0.28125, respectively. Meanwhile, the allelopathic effects of these sesquiterpenes on Arabidopsis seed germination were also tested. Compounds 5, 7, 17 and 18 retarded the seed germination of Arabidopsis with IC50 values ranging from 9.1 to 41 μg/mL, while other compounds showed no obvious inhibitory effects.

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