scholarly journals DPP-IV Inhibitory Potentials of Flavonol Glycosides Isolated from the Seeds of Lens culinaris: In Vitro and Molecular Docking Analyses

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1998 ◽  
Author(s):  
Bo-Ram Kim ◽  
Hyo Kim ◽  
Inhee Choi ◽  
Jin-Baek Kim ◽  
Chang Jin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Lens Culinaris ◽  
Binding Pocket ◽  
Catalytic Triad ◽  
Flavonol Glycosides ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Dpp Iv

Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides (1–3) were isolated from the seeds of Lens culinaris Medikus (Fabaceae) and tested for their DPP-IV–inhibitory activity. We demonstrated for the first time, that compounds 1–3 inhibited DPP-IV activity in a concentration-dependent manner in our in vitro bioassay system. In addition, molecular docking experiments of compounds 1–3 within the binding pocket of DPP-IV were conducted. All investigated compounds readily fit within the active sites of DPP-IV, in low-energy conformations characterized by the flavone core structure having optimal electrostatic attractive interactions with the catalytic triad residues of DPP-IV.

scholarly journals Dipeptidyl-Peptidase IV Converts Intact B-Type Natriuretic Peptide into Its des-SerPro Form

2006 ◽  
Vol 52 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Inger Brandt ◽  
Anne-Marie Lambeir ◽  
Jean-Marie Ketelslegers ◽  
Marc Vanderheyden ◽  
Simon Scharpé ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Ex Vivo ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Amino Terminal ◽  
Dpp Iv

Abstract Background: Analysis of plasma B-type natriuretic peptide (BNP) has suggested the in vivo formation of a truncated form, BNP (3–32), also called des-SerPro-BNP. The objectives of this study were to investigate (a) whether BNP and other natriuretic peptides are truncated by dipeptidyl-peptidase IV (DPP IV/CD26; EC 3.4.14.5) and (b) whether this truncation affects the susceptibility to cleavage by neutral endopeptidase (NEP; EC 3.4.24.11). Methods: Human BNP (1–32), A-type natriuretic peptide 1–28 (ANP 1–28), and related peptides were incubated with purified DPP IV and with human plasma. In addition, BNP (1–32), BNP (3–32), and ANP (1–28) were subjected to hydrolysis by NEP. Cleavage products were analyzed by mass spectrometry. Results: BNP (1–32) was cleaved by purified DPP IV with a specificity constant of 0.37 × 106 L · mol−1 · s−1. The DPP IV activity in EDTA-plasma was able to truncate BNP (1–32) ex vivo. Addition of Vildagliptin, a specific DPP IV inhibitor, prevented this truncation in a concentration-dependent manner. Under in vitro circumstances in which ANP was hydrolyzed extensively, BNP (1–32) and BNP (3–32) were very resistant to NEP-mediated cleavage. Conclusions: DPP IV cleaves BNP (1–32) with an efficiency higher than or comparable to several known in vivo substrates of the enzyme. Even after loss of the amino-terminal dipeptide, BNP remains highly resistant to cleavage by NEP.

Exploring the effect of Polyphyllin I on hepatitis B virus-related liver cancer through network pharmacology and in vitro experiments

2021 ◽  
Vol 24 ◽  
Author(s):  
Shuxian Yu ◽  
Wenhui Gao ◽  
Puhua Zeng ◽  
Chenglong Chen ◽  
Zhuo Liu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Cancer ◽  
Mechanism Of Action ◽  
Active Ingredient ◽  
Vehicle Group ◽  
Network Pharmacology ◽  
Dependent Manner ◽  
In Vitro Experiments ◽  
Concentration Dependent Manner

Aim and Objective: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. Materials and Methods: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. Results: Bioinformatics analysis found that PPI had totally 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 μmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). Conclusion: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

scholarly journals Discovery of a AhR flavonoid agonist that counter-regulates ACE2 expression in rodent models of inflammation and attenuates ACE2-SARS-CoV2 interaction in vitro

2021 ◽  
Author(s):  
Michele Biagioli ◽  
Silvia Marchianò ◽  
Rosalinda Roselli ◽  
Cristina Di Giorgio ◽  
Rachele Bellini ◽  
...  
Keyword(s):  
Viral Entry ◽  
Intestinal Inflammation ◽  
Binding Pocket ◽  
Docking Studies ◽  
Spike Protein ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Fatty Acid Binding

AbstractThe severe acute respiratory syndrome (SARS)-CoV-2, a newly emerged coronavirus first identified in 2019, is the pathogenetic agent od Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE) 2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of ACE2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin, a natural flavonoid bind and activates the Aryl hydrocarbon Receptor (AhR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent DSS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of ACE2 mRNA expression. Colon levels of ACE2 mRNA were directly correlated with TNFα mRNA levels. In contrast to ACE2 the angiotensin 1-7 receptor MAS was downregulated in the inflamed tissues. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV2 Spike protein to ACE2 and reduces the SARS-CoV2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner.

scholarly journals Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 414
Author(s):  
Sania Bashir ◽  
Ishfaq Ahmad Ahanger ◽  
Anas Shamsi ◽  
Mohamed F. Alajmi ◽  
Afzal Hussain ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Rayleigh Scattering ◽  
Binding Pocket ◽  
Dependent Manner ◽  
Thermal Aggregation ◽  
Concentration Dependent Manner ◽  
In Silico Studies ◽  
Vis Spectroscopy ◽  
Amyloid Fibrillation

Protein aggregation and misfolding are some of the most challenging obstacles, customarily studied for their association with amyloid pathologies. The mechanism of amyloid fibrillation development is a dynamic phenomenon involving various factors such as the intrinsic properties of protein and the physical and chemical environmental conditions. The purpose of this study was to see the thermal aggregation profile of alpha-lactalbumin (α-LA) and to delineate the effect of trehalose on its aggregation profile. α-LA was subjected to thermal aggregation at high concentrations. UV-Vis spectroscopy, a turbidity assay, intrinsic fluorescence, Rayleigh scattering and a thioflavin T (ThT) assay explained the steady outcomes that 1 M trehalose repressed α-LA aggregation in the most effective way followed by 0.75 M and 0.5 M and to a significantly lesser degree by 0.25 M. Multi spectroscopic obser Sania Bashir ations were further entrenched by microscopy. Transmission electron microscopy confirmed that in the presence of its higher concentration, trehalose hinders fibril development in α-LA. In vitro studies were further validated by in silico studies. Molecular docking analysis indicated that trehalose occupied the binding pocket cavity of α-LA and offered several significant interactions, including H-bonds with important residues. This study provides a platform for trehalose in the therapeutic management of protein aggregation-related diseases.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

1'-methylspiro[indoline-3,4'-piperidine] Derivatives: Design, Synthesis, Molecular Docking and Anti-tumor Activity Studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Junjian Li ◽  
Lianbao Ye ◽  
Yuanyuan Wang ◽  
Ying Liu ◽  
Xiaobao Jin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Active Sites ◽  
Biological Activities ◽  
Significant Inhibition ◽  
Alkaline Condition ◽  
Discovery Studio ◽  
Hela Cell Lines ◽  
Antiproliferative Activities

Background: Spirocyclic indoline compounds widely exist in numerous natural products with good biological activities and some drug molecules in many aspects. In recent years, it has attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry. Objective: In this study, we focused on designing and synthesizing a set of novel 1'-H-spiro[indole-3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking. Method: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its sulfonyl derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cells by MTT assay. We performed the CDOCKER module in Discovery Studio 2.5.5 software for molecular modeling of compound B5, and investigated the binding of compound B5 with the target proteins from PDB database. Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cells, in which compound B5 with chloride atom as electron-withdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cells (IC50=30.03±0.43 μg/mL). By binging of the prominent bioactive compound B5 to CDK, c-Met, EGFR protein crystals, The binding energy of B5 with these three types receptors are -44.3583 kcal/mol, - 38.3292 kcal/mol, -33.3653 kcal/mol respectively. Conclusion: Six 1'-methylspiro[indoline-3,4'-piperidine] derivatives were synthesized and evaluated against BEL-7402, A- 549, HeLa cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking revealed that B5 showed good affinity by the good fitting between B5 and these three targets with amino acid residues in active sites which encourage us to conduct further evaluation such as the kinase experiment.

Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells

2020 ◽  
Vol 16 (3) ◽  
pp. 358-362
Author(s):  
Renan S. Teixeira ◽  
Paulo H.D. Carvalho ◽  
Jair A.K. Aguiar ◽  
Valquíria P. Medeiros ◽  
Ademar A. Da Silva Filho ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Crude Extract ◽  
Hepg2 Cells ◽  
Liver Carcinoma ◽  
Adhesion Assay ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Arctium Lappa ◽  
Nih 3T3

Background: Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma (HepG2) and fibroblasts (NIH/3T3). Methods: Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity. Results: Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a concentration-dependent manner, when compared with control. Conclusion: These results suggest a promising pharmacological activity for arctigenin as an antiproliferative compound.

Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

2019 ◽  
Vol 16 (6) ◽  
pp. 696-710
Author(s):  
Mahmoud Balbaa ◽  
Doaa Awad ◽  
Ahmad Abd Elaal ◽  
Shimaa Mahsoub ◽  
Mayssaa Moharram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Active Sites ◽  
Biological Activities ◽  
Imidazole Ring ◽  
Quantitative Structure Activity Relationship ◽  
Binding Interaction ◽  
Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

scholarly journals Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances

2021 ◽  
Vol 22 (13) ◽  
pp. 6785
Author(s):  
Valeria Sogos ◽  
Paola Caria ◽  
Clara Porcedda ◽  
Rafaela Mostallino ◽  
Franca Piras ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell ◽  
In Vitro Study ◽  
Dependent Manner ◽  
Novel Psychoactive Substances ◽  
Psychoactive Substances ◽  
Concentration Dependent Manner ◽  
Mechanisms Of Toxicity ◽  
Neuronal Cell Lines

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.

Sign in / Sign up

Export Citation Format

Share Document