scholarly journals In Silico and In Vitro Analysis of Multifunctionality of Animal Food-Derived Peptides

Foods ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 991 ◽  
Author(s):  
Lourdes Amigo ◽  
Daniel Martínez-Maqueda ◽  
Blanca Hernández-Ledesma
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Vitro Study ◽  
In Silico Analysis ◽  
Integrated Approach ◽  
In Vitro Assays ◽  
Metabolic Disturbances ◽  
Ace Inhibitory

Currently, the associations between oxidative stress, inflammation, hypertension, and metabolic disturbances and non-communicable diseases are very well known. Since these risk factors show a preventable character, the searching of food peptides acting against them has become a promising strategy for the design and development of new multifunctional foods or nutraceuticals. In the present study, an integrated approach combining an in silico study and in vitro assays was used to confirm the multifunctionality of milk and meat protein-derived peptides that were similar to or shared amino acids with previously described opioid peptides. By the in silico analysis, 15 of the 27 assayed peptides were found to exert two or more activities, with Angiotensin-converting enzyme (ACE) inhibitory, antioxidant, and opioid being the most commonly found. The in vitro study confirmed ACE-inhibitory and antioxidant activities in 15 and 26 of the 27 synthetic peptides, respectively. Four fragments, RYLGYLE, YLGYLE, YFYPEL, and YPWT, also demonstrated the ability to protect Caco-2 and macrophages RAW264.7 cells from the oxidative damage caused by chemicals. The multifunctionality of these peptides makes them promising agents against oxidative stress-associated diseases.

scholarly journals The Bioactivity Prediction of Peptides from Tuna Skin Collagen Using Integrated Method Combining In Vitro and In Silico

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2739
Author(s):  
Liza Devita ◽  
Hanifah Nuryani Lioe ◽  
Mala Nurilmala ◽  
Maggy T. Suhartono
Keyword(s):  
Antioxidant Activity ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Silico Analysis ◽  
Weight Fraction ◽  
Amino Acid Sequences ◽  
Skin Collagen ◽  
Dpph Method ◽  
Peptide Fractions

The hydrolysates and peptide fractions of bigeye tuna (Thunnus obesus) skin collagen have been successfully studied. The hydrolysates (HPA, HPN, HPS, HBA, HBN, HBS) were the result of the hydrolysis of collagen using alcalase, neutrase, and savinase. The peptide fractions (PPA, PPN, PPS, PBA, PBN, PBS) were the fractions obtained following ultrafiltration of the hydrolysates. The antioxidant activities of the hydrolysates and peptide fractions were studied using the DPPH method. The effects of collagen types, enzymes, and molecular sizes on the antioxidant activities were analyzed using profile plots analysis. The amino acid sequences of the peptides in the fraction with the highest antioxidant activity were analyzed using LC-MS/MS. Finally, their bioactivity and characteristics were studied using in silico analysis. The hydrolysates and peptide fractions provided antioxidant activity (6.17–135.40 µmol AAE/g protein). The lower molecular weight fraction had higher antioxidant activity. Collagen from pepsin treatment produced higher activity than that of bromelain treatment. The fraction from collagen hydrolysates by savinase treatment had the highest activity compared to neutrase and alcalase treatments. The peptides in the PBN and PPS fractions of <3 kDa had antidiabetic, antihypertensive and antioxidant activities. In conclusion, they have the potential to be used in food and health applications.

scholarly journals Berberine Derivatives as Pseudomonas aeruginosa MexXY-OprM Inhibitors: Activity and In Silico Insights

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6644
Author(s):  
Giorgia Giorgini ◽  
Gianmarco Mangiaterra ◽  
Nicholas Cedraro ◽  
Emiliano Laudadio ◽  
Giulia Sabbatini ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
In Silico ◽  
Rational Design ◽  
Specific Binding ◽  
In Silico Analysis ◽  
In Vitro Assays ◽  
Binding Modes ◽  
Starting Point ◽  
Berberine Derivatives

The natural alkaloid berberine has been demonstrated to inhibit the Pseudomonas aeruginosa multidrug efflux system MexXY-OprM, which is responsible for tobramycin extrusion by binding the inner membrane transporter MexY. To find a structure with improved inhibitory activity, we compared by molecular dynamics investigations the binding affinity of berberine and three aromatic substituents towards the three polymorphic sequences of MexY found in P. aeruginosa (PAO1, PA7, and PA14). The synergy of the combinations of berberine or berberine derivatives/tobramycin against the same strains was then evaluated by checkerboard and time-kill assays. The in silico analysis evidenced different binding modes depending on both the structure of the berberine derivative and the specific MexY polymorphism. In vitro assays showed an evident MIC reduction (32-fold and 16-fold, respectively) and a 2–3 log greater killing effect after 2 h of exposure to the combinations of 13-(2-methylbenzyl)- and 13-(4-methylbenzyl)-berberine with tobramycin against the tobramycin-resistant strain PA7, a milder synergy (a 4-fold MIC reduction) against PAO1 and PA14, and no synergy against the ΔmexXY strain K1525, confirming the MexY-specific binding and the computational results. These berberine derivatives could thus be considered new hit compounds to select more effective berberine substitutions and their common path of interaction with MexY as the starting point for the rational design of novel MexXY-OprM inhibitors.

scholarly journals In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis

2021 ◽  
Vol 14 (12) ◽  
pp. 1337
Author(s):  
Akhtar Ali ◽  
YoungJoon Park ◽  
Jeonghoon Lee ◽  
Hyo-Jin An ◽  
Jong-Sik Jin ◽  
...  
Keyword(s):  
In Silico ◽  
In Vitro Study ◽  
In Silico Analysis ◽  
In Vivo Studies ◽  
Binding Potential ◽  
New Variety ◽  
Chondrocyte Hypertrophy ◽  
Active Compounds

Osteoarthritis (OA) is a common degenerative joint disorder that affects joint function, mobility, and pain. The release of proinflammatory cytokines stimulates matrix metalloproteinases (MMPs) and aggrecanase production which further induces articular cartilage degradation. Hypertrophy-like changes in chondrocytes are considered to be an important feature of OA pathogenesis. A Glycyrrhiza new variety, Wongam (WG), was developed by the Korea Rural Development Administration to enhance the cultivation and quality of Glycyrrhizae Radix et Rhizoma (licorice). This study examined the regulatory effect of WG against hypertrophy-like changes such as RUNX2, Collagen X, VEGFA, MMP-13 induction, and Collagen II reduction induced by IL-1β in SW1353 human chondrocytes. Additionally, in silico methods were performed to identify active compounds in licorice to target chondrocyte hypertrophy-related proteins. WG showed inhibitory effects against IL-1β-induced chondrocyte hypertrophy by regulating both HDAC4 activation via the PTH1R/PKA/PP2A pathway and the SOX9/β-catenin signaling pathway. In silico analysis demonstrated that 21 active compounds from licorice have binding potential with 11 targets related to chondrocyte hypertrophy. Further molecular docking analysis and in vivo studies elicited four compounds. Based on HPLC, isoliquiritigenin and its precursors were identified and quantified. Taken together, WG is a potential therapeutic agent for chondrocyte hypertrophy-like changes in OA.

scholarly journals Gamma-hexalactone flavoring causes DNA lesion and modulates cytokines secretion at non-cytotoxic concentrations

2019 ◽  
Vol 20 (S1) ◽  
Author(s):  
Luísa Zuravski ◽  
Taiane A. Escobar ◽  
Elizandra G. Schmitt ◽  
Queila D. F. Amaral ◽  
Fávero R. Paula ◽  
...  
Keyword(s):  
Comet Assay ◽  
In Silico ◽  
In Silico Analysis ◽  
Computational Prediction ◽  
Negative Control ◽  
Alcoholic Beverages ◽  
In Vitro Assays ◽  
In Vitro Tests ◽  
Dna Comet Assay

Abstract Background The γ-hexalactone is a flavoring agent for alcoholic beverages, teas, breads, dairy products, coffees, buttery products among others. It presents low molecular weight and exhibits sweet fruity aroma with nuances of nuts. As far as we know, both literature and government regulations have gaps regarding the safe use of the γ-hexalactone. In this context, the main objective of this work was to evaluate the effects of γ-hexalactone through in silico and in vitro approaches. Methods The in silico analysis was performed through four free online platforms (admetSAR, Osiris Property Explorer®, pkCSM platform and PreADMET) and consisted of comparative structural analysis with substances present in databases. The computational prediction was performed in the sense of complement and guide the in vitro tests. Regarding in vitro investigations, screening of cytotoxicity (assessed by cell proliferation and viability parameters) in lymphocytes exposed to γ-hexalactone for 72 h were carried out previously to determine non-cytotoxic concentrations. Following this screening, concentrations of 5.15, 0.515, and 0.0515 μM were selected for the study of the respective potentials: genotoxic (assessed by DNA comet assay), chromosomal mutation (analysis of micronucleus frequency) and immunomodulatory (cytokine quantification using ELISA immunoassay). The results of in vitro assays were compared by one-way analysis of variance (ANOVA), followed by Bonferroni’s post hoc test, conducted by statistic software. Results The platform PreADMET pointed out that γ-hexalactone is potentially mutagenic and carcinogenic. The comet assay data corroborate with these results demonstrating that γ-hexalactone at 5.15 μM caused lymphocytes DNA damage. In relation to cytokine secretion, the results indicate that lymphocytes were activated by γ-hexalactone at non-cytotoxic concentrations, involving an increase in the IL-1 levels in all tested concentrations, ranging from approximately 56 to 93%. The γ-hexalactone only at 5.15 μM induced increase in the levels of IL-6 (~ 60%), TNF-α (~ 68%) and IFN-γ (~ 29%), but decreased IL-10 (~ 46%) in comparison with the negative control (p < 0.05). No change was observed in total lymphocytes or in cell viability at the concentrations tested. Conclusions In summary, the γ-hexalactone demonstrated immunomodulatory and genotoxic effects at non-cytotoxic concentrations in healthy lymphocytes.

scholarly journals Integration of in silico and in vitro approach to reveal the anticancer efficacy of Virgin Coconut Oil

CORD ◽  
2020 ◽  
Vol 36 ◽  
pp. 1-9
Author(s):  
Babita Pruseth ◽  
Silvi Banerjee ◽  
Amit Ghosh
Keyword(s):  
In Silico ◽  
Antioxidant Properties ◽  
Coconut Oil ◽  
In Vitro Study ◽  
In Silico Analysis ◽  
Virgin Coconut Oil ◽  
Anticancer Efficacy ◽  
Target Proteins ◽  
The Impact

Background: Virgin coconut oil (VCO) has antioxidant properties and is being increasingly used as nutraceuticals and cosmeceuticals. It also has a long history of ethnopharmacological use. Anticancer effect of VCO has been reported in several articles. The main bottleneck of exploring the anticancer efficacy of VCO is the difficulty in identification and validation of target proteins and their regulated pathways. Aim: The work plan was in-silico analysis using Comparative Toxicogenomics Database (CTD) and STRING. CTD curated and integrated data for more than 5700 gene-disease and 2000 chemical-disease relationship. Medium Chain Fatty Acids (MCFAs) from VCO like Lauric acid, Caprylic Acid, Capric Acid, and Myristic acid can target almost 17 cancer-associated proteins. Method: Using in silico and in vitro approach, an attempt was made to identify the target proteins and their pathways regulated by VCO. Result: We analyze curated and inferred VCO-gene expression data and illustrate the impact of VCO exposure on cancer-related gene network and molecular function. In enriched pathway analysis, it has been evident that all of them are the part of different cancer-associated pathways (Neoplasms, Digestive System Neoplasms, Urogenital Neoplasms, Liver Neoplasms). This response may mimic the biological response to VCO. In silico result was tested by in vitro study and VCO kill the Human hepatocellular carcinoma cell lines (hepG2). Conclusion: Based on the findings of this study and several published studies it is proposed that a VCO may have immense potential as a botanical product against cancer.

scholarly journals In Silico Analysis and In Vitro Characterization of the Bioactive Profile of Three Novel Peptides Identified from 19 kDa α-Zein Sequences of Maize

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5405
Author(s):  
Jorge L. Díaz-Gómez ◽  
Ines Neundorf ◽  
Laura-Margarita López-Castillo ◽  
Fabiola Castorena-Torres ◽  
Sergio O. Serna-Saldívar ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Structural Model ◽  
Solid Phase ◽  
Antioxidant Activities ◽  
Ace Inhibitory Activity ◽  
Helical Structures ◽  
In Vitro Characterization ◽  
Ace Inhibitory

In this study, we characterized three novel peptides derived from the 19 kDa α-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed α-helical structures and had positive and negative electrostatic potential surfaces (range of −1 to +1). According to the in silico algorithms, the peptides displayed low probabilities for cytotoxicity (≤0.05%), cell penetration (10–33%) and antioxidant activities (9–12.5%). Instead, they displayed a 40% probability for angiotensin-converting enzyme (ACE) inhibitory activity. For in vitro characterization, peptides were synthesized by solid phase synthesis and tested accordingly. We assumed α-helical structures for 19ZP1 and 19ZP2 under hydrophobic conditions. The peptides displayed antioxidant activity and ACE-inhibitory activity, with 19ZP1 being the most active. Our results highlight that the 19 kDa α-zein sequences could be explored as a source of bioactive peptides, and indicate that in silico approaches are useful to predict peptide bioactivities, but more structural analysis is necessary to obtain more accurate data.

scholarly journals In Silico and In Vitro Analysis of Major Cannabis-Derived Compounds as Fatty Acid Amide Hydrolase Inhibitors

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 48
Author(s):  
Emanuele Criscuolo ◽  
Maria Laura De Sciscio ◽  
Filomena Fezza ◽  
Mauro Maccarrone
Keyword(s):  
Fatty Acid ◽  
In Silico ◽  
Therapeutic Potential ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Integrated Approach ◽  
In Vitro Assays ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Accumulated evidence suggests that enhancing the endocannabinoid (eCB) tone, in particular of anandamide (N-arachidonoylethanolamine, AEA), has therapeutic potential in many human diseases. Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme principally responsible for the degradation of AEA, and thus it represents a relevant target to increase signaling thereof. In recent years, different synthetic and natural compounds have been developed and tested on rat FAAH, but little is known of their effect on the human enzyme. Here, we sought to investigate six major cannabis-derived compounds to compare their action on rat and human FAAHs. To this aim, we combined an in silico analysis of their binding mode and affinity, with in vitro assays of their effect on enzyme activity. This integrated approach allowed to disclose differences in efficacy towards rat and human FAAHs, and to highlight the role of key residues involved in the inhibition of both enzymes. This study suggests that the therapeutic efficacy of compounds targeted towards FAAH should be always tested in vitro on both rat and human enzymes.

Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents: Design, Synthesis, Biological Evaluation, SAR and in silico Studies

2021 ◽  
Vol 27 ◽  
Author(s):  
Bharti Rajesh Kumar Shyamlal ◽  
Manas Mathur ◽  
Dharmendra K. Yadav ◽  
Irina V. Mashevskaya ◽  
Mohamed El-Shazly ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Silico Analysis ◽  
Antiplatelet Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
In Silico Studies

Background: Several natural/synthetic molecules having structure similar to 1H-isochromen-1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of molecular framework, have been explored for their antioxidant or antiplatelet activities. Introduction: Based on literature, a new prototype i.e., 3-phenyl-1H-isochromen-1-ones based compounds have been rationalized to possess both antioxidant as well as antiplatelet activities. Consequently, no reports are available regarding its inhibition either by cyclooxygenase-1 (COX-1) enzyme or by arachidonic acid (AA)-induced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxidant and antiplatelet agents. Methods: The goal of this work to identify new 3-phenyl-1H-isochromen-1-ones based compounds via synthesis of a series of analogues and performing in vitro antioxidant as well as AA-induced antiplatelet activities and then, identification of potent compounds by SAR and molecular docking studies. Results: Out of all synthesized 3-phenyl-1H-isochromen-1-ones analogues, five compounds showed 7-folds to 16-folds highly potent antioxidant activities than ascorbic acid. Altogether, ten 3-phenyl-1H-isochromen-1-one analogues displayed antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Almost, all the 3-phenyl-1H-isochromen-1-one analogues exhibited potent AA-induced antiplatelet activity; few of them displayed 7-folds more activity as compared to aspirin. Further, in silico analysis validated the wet results. Conclusion: We disclose the first detailed study for the identification of 3-phenyl-1H-isochromen-1-one analogues as highly potent antioxidant as well as antiplatelet agents. The article describes the scaffold designing, synthesis, bioevaluation, structure-activity relationship and in silico studies of pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.

Sign in / Sign up

Export Citation Format

Share Document