Enzymatic release of dipeptidyl peptidase-4(DPP-4) inhibitors from pigeon pea proteins: In silico and wet-lab assessments

2020 ◽  
Author(s):  
Ruth Boachie
Keyword(s):  
In Silico ◽  
Pigeon Pea ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Wet Lab ◽  
Pea Proteins

scholarly journals Molecular Docking Studies of Phenolic Compounds from Syzygium cumini with Multiple Targets of Type 2 Diabetes

2018 ◽  
Vol 6 (2) ◽  
pp. 125-133
Author(s):  
Ajmer Singh Grewal ◽  
Neelam Sharma ◽  
Sukhbir Singh ◽  
Sandeep Arora
Keyword(s):  
Type 2 Diabetes ◽  
Phenolic Compounds ◽  
Side Effects ◽  
In Silico ◽  
Glycogen Synthase ◽  
Dipeptidyl Peptidase ◽  
Docking Studies ◽  
Multiple Targets ◽  
Dipeptidyl Peptidase 4

Treatment of type 2 diabetes without any side effects is still a challenge to the medical system. This leads to increasing demand for natural products with antidiabetic activity with fewer side effects. Syzygium cumini is a traditional herbal medicinal plant and is reported to possess a variety of pharmacological actions. It contains various types of chemical constituents including terpenoids, tannins, anthocyanins, flavonoids and other phenolic compounds. Some flavonoids and other phenolic compounds from S. cumini were reported in literature to have type 2 antidiabetic potential. The main objective of the current investigation was in silico screening of some phenolic compounds from S. cumini against multiple targets associated with type 2 diabetes to explore the mechanism of antidiabetic action and prediction of binding mode using molecular docking studies. In silico docking studies were performed for the selected molecules in the binding site of multiple targets associated with type 2 diabetes (α-glucosidas , dipeptidyl peptidase 4, glycogen synthase kinase 3, glucokinase and glucagon receptor). Amongst the compounds tested in silico, rutin showed appreciable binding with multiple targets of type 2 diabetes including α-glucosidase, dipeptidyl peptidase 4, glycogen synthase kinase 3, and glucagon receptor. Catechin was found to inhibit both α-glucosidase, and dipeptidyl peptidase 4. This information can be utilized for the design and development of potent multi-functional candidate drugs with minimal side effects for type 2 diabetes therapeuticsa.

scholarly journals Docking Molekular dari Trigonella foenum- graceum sebagai Antidiabetes menggunakan molegro virtual docking.

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Andri Prasetiyo Prasetiyo
Keyword(s):  
Sugar Beet ◽  
In Silico ◽  
Dipeptidyl Peptidase ◽  
Peroxisome Proliferator ◽  
Dipeptidyl Peptidase 4 ◽  
Alpha Glucosidase

Trigonella foenum-graceum atau fenugreek digunakan secara luas  sebagai obat tradisional  untuk pengobatan diabetes tetapi mekanisme kerjanya masih belum jelas. Penelitian bertujuan memprediksi senyawa dalam fenugreek yang berkhasiat sebagai antidiabetes secara in-silico dengan menggunakan perangkat lunak Molegro Virtual Docking . Docking dilakukan 10 Senyawa uji dalam fenugreek yaitu 4-hidroxyisoleucine, coumarine, diosgenin, galactomannan, isovitexin, quarcetin, tigogenin, trigoneline, vitexin dan yamogenin dengan 3 reseptor yaitu sugar beet alpha-glucosidase- (PDB ID : 3W37), human dipeptidyl peptidase-4 (PDB ID : 2RGU), human peroxisome proliferator activated gamma (PDB: 2PRG) serta senyawa pembanding acarbose, linagliptin dan rosiglitazone. Dari 10 senyawa uji, galactomanann  memiliki nilai Rerank Score/RS paling rendah di dua reseptor yaitu alpha glucosidase dan peroxisome proliferator activated gamma dengan nilai berturut turut -116,558kkal/mol dan -131.184kkal/mol dan nilai RS acarbose -113.595kkal/mol dan rosiglitazone -124.537kkal/mol . Dari 10 senyawa uji, vitexin memiliki nilai RS paling rendah direseptor dipeptidyl peptidase-4 dengan nilai RS -86.7288 kkal/mol dan nilai RS linagliptin 109.665kkal/mol. Berdasarkan nilai RS, galactomannan diprediksi memiliki aktivitas antidiabetes yang bekerja pada reseptor alpha-glucosidase dan peroxisome proliferator activated gamma sedangkan vitexin diprediksi memiliki aktivitas antidiabetes yang bekerja pada reseptor dipeptidyl peptidase-4.

scholarly journals An Integrated In Silico and In Vitro Assays of Dipeptidyl Peptidase-4 and α-Glucosidase Inhibition by Stellasterol from Ganoderma australe

2019 ◽  
Vol 87 (3) ◽  
pp. 21 ◽  
Author(s):  
Krisyanti Budipramana ◽  
Junaidin Junaidin ◽  
Komar Ruslan Wirasutisna ◽  
Yanatra Budi Pramana ◽  
Sukrasno Sukrasno
Keyword(s):  
In Silico ◽  
Dipeptidyl Peptidase ◽  
Antidiabetic Activity ◽  
Resonance Spectroscopy ◽  
Dipeptidyl Peptidase 4 ◽  
13C Nuclear Magnetic Resonance ◽  
Study Results ◽  
In Silico Study ◽  
Ganoderma Australe ◽  
Isolated Compound

Background: Ganoderma fungus is rich in terpenoids. These compounds are known for their anti-hyperglycemic activities. However, the study of terpenoids as the secondary metabolite from Ganoderma as a dipeptidyl peptidase-4 (DPP-4) inhibitor remains unexplored. In addition, we examined the α-glucosidase inhibition activity. Objective: This study aimed to isolate the major terpenoid from non-laccate Ganoderma and examined its inhibitor activity on DPP-4 and α-glucosidase enzymes, and its interaction. Methods: The compound was isolated using column chromatography from Ganoderma australe. The structure of the isolated compound was confirmed by 1H and 13C nuclear magnetic resonance spectroscopy, while the inhibitory activity was evaluated using an enzymatic assay. The interaction of the isolated compound with DPP-4 and α-glucosidase enzymes was investigated using an in silico study. Results: The isolated compound was identified as stellasterol; IC50 values for DPP-4 and α-glucosidase inhibitor were 427.39 µM and 314.54 µM, respectively. This study revealed that the inhibitory effect of stellasterol on DPP-4 enzyme is through hydrophobic interaction, while the α-glucosidase enzyme is due to the interaction with six amino acids of the enzyme. Conclusion: Stellasterol is the major component of the steroid from G. australe. Enzyme inhibitory assay and in silico study suggest that stellasterol may contribute antidiabetic activity with a mechanism closer to acarbose rather than to sitagliptin.

scholarly journals IN SILICO APPROACH FOR SCREENING OF THE INDONESIAN MEDICINAL PLANTS DATABASE TO DISCOVER POTENTIAL DIPEPTIDYL PEPTIDASE-4 INHIBITORS

2020 ◽  
pp. 60-68
Author(s):  
AULIA FARKHANI ◽  
RANI SAURIASARI ◽  
ARRY YANUAR
Keyword(s):  
Medicinal Plants ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Pharmacophore Model ◽  
Dipeptidyl Peptidase ◽  
Operating Characteristics ◽  
Dipeptidyl Peptidase 4 ◽  
Therapeutic Drugs ◽  
Dipeptidyl Peptidase 4 Inhibitors

Background: Dipeptidyl peptidase-4 (DPP4) is an enzyme responsible for inactivating the hormone incretin, which potentiates insulin secretion andglucagon inhibition; inhibitors of DPP4 are used as therapeutic drugs for type-2 diabetes.Objective: In this study, we evaluated potential DPP4 inhibitors from the Indonesian Medicinal Plants Database using an in silico approach.Methods: A ligand-based pharmacophore model was used for screening the database using LigandScout 4.2. This model was validated using severalparameters of enrichment metrics, including receiver operating characteristics, area under curve (AUC), and enrichment factor (EF). Hit compoundswere also docked with DPP4 to calculate the free binding energy and analyze the interaction between the ligand and DPP4. In addition, bioavailabilityand medicinal chemistry predictions were performed for the hit compounds.Results: The best pharmacophore model demonstrated AUC100% and EF1% values of 0.82 and 33.8, respectively. The pharmacophore features of themodel included hydrogen bond donors, hydrogen bonds, hydrophobic interactions, and positive ionization areas. Based on our results of virtualscreening and molecular docking, six hit compounds were ultimately identified, namely, L-noradrenaline, octopamine, Nb-demethylechitamine, alliin,isoalliin, and subaphylline.Conclusion: Collectively, our findings indicate that subaphylline is the most promising compound for further studies, including in vitro and in vivoexperiments and those focused on molecular dynamics and structural modification.

Docking Molekular dari Trigonella foenum-graceum sebagai Antidiabetes menggunakan Molegro Virtual Docking

2019 ◽  
Vol 4 (2) ◽  
pp. 74-80
Author(s):  
Andri Prasetiyo ◽  
Esti Mumpuni ◽  
Raymond R. Tjandrawinata
Keyword(s):  
Sugar Beet ◽  
In Silico ◽  
Dipeptidyl Peptidase ◽  
Peroxisome Proliferator ◽  
Dipeptidyl Peptidase 4 ◽  
Alpha Glucosidase

Trigonella foenum-graceum atau fenugreek digunakan secara luas  sebagai obat tradisional  untuk pengobatan diabetes tetapi mekanisme kerjanya masih belum jelas. Penelitian bertujuan memprediksi senyawa dalam fenugreek yang berkhasiat sebagai antidiabetes secara in-silico dengan menggunakan perangkat lunak Molegro Virtual Docking . Docking dilakukan 10 Senyawa uji dalam fenugreek yaitu 4-hidroxyisoleucine, coumarine, diosgenin, galactomannan, isovitexin, quarcetin, tigogenin, trigoneline, vitexin dan yamogenin dengan 3 reseptor yaitu sugar beet alpha-glucosidase- (PDB ID : 3W37), human dipeptidyl peptidase-4 (PDB ID : 1X70), human peroxisome proliferator activated gamma (PDB: 2PRG) serta senyawa pembanding acarbose, sitagliptin dan rosiglitazone. Dari 10 senyawa uji, galactomanann  memiliki nilai Rerank Score/RS paling rendah di dua reseptor yaitu alpha glucosidase dan peroxisome proliferator activated gamma dengan nilai berturut turut -116.56 kcal/mol dan -131.18 kcal/mol dan nilai RS acarbose -113.60 kcal/mol dan rosiglitazone -124.54 kcal/mol . Dari 10 senyawa uji, tigogenin memiliki nilai RS paling rendah direseptor dipeptidyl peptidase-4 dengan nilai RS -86.54 kcal/mol dan nilai RS sitagliptin -87.02 kcal/mol. Berdasarkan nilai RS, galactomannan diprediksi memiliki aktivitas antidiabetes yang bekerja pada reseptor alpha-glucosidase dan peroxisome proliferator activated gamma sedangkan tigogenin diprediksi memiliki aktivitas antidiabetes yang bekerja pada reseptor dipeptidyl peptidase-4.

scholarly journals The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from in silico to in vivo

2019 ◽  
Vol 10 ◽  
pp. 204062231987530 ◽  
Author(s):  
Shian-Ren Lin ◽  
Chia-Hsiang Chang ◽  
May-Jwan Tsai ◽  
Henrich Cheng ◽  
Jian-Chyi Chen ◽  
...  
Keyword(s):  
Blood Glucose ◽  
In Silico ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Cell Assays ◽  
Insulin Activity ◽  
Pros And Cons ◽  
Glucagon Like Peptide 1

Dipeptidyl peptidase IV (DPP-4), an incretin glucagon-like peptide-1 (GLP-1) degrading enzyme, contains two forms and it can exert various physiological functions particular in controlling blood glucose through the action of GLP-1. In diabetic use, the DPP-4 inhibitor can block the DDP-4 to attenuate GLP-1 degradation and prolong GLP-1 its action and sensitize insulin activity for the purpose of lowering blood glucose. Nonetheless the adverse effects of DPP-4 inhibitors severely hinder their clinical applications, and notably there is a clinical demand for novel DPP-4 inhibitors from various sources including chemical synthesis, herbs, and plants with fewer side effects. In this review, we highlight various strategies, namely computational biology ( in silico), in vitro enzymatic and cell assays, and in vivo animal tests, for seeking natural DPP-4 inhibitors from botanic sources including herbs and plants. The pros and cons of all approaches for new inhibitor candidates or hits will be under discussion.

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