Identification of PPAR β/δ agonists using a drug-repurposing approach by computational HTVS and molecular docking/ dynamics simulation DOI Creative Commons
Sumit K. Mandal,

Mohammed Muzaffar-Ur-Rehman,

Sonakshi Puri

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 11, 2023

Abstract Peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating carbohydrate and lipid metabolism are considered as significant targets for treating metabolic syndrome cancers. There is need to identify new bioactive ligands that can activate specific PPAR subtypes, particularly PPARβ/δ, which less studied compared other isoforms (α γ). Here, the ZINC database of clinically approved drugs was screened target PPARβ/δ receptor, through virtual screening followed by molecular docking dynamics (MD) simulation. Among ligands, top five with strong binding affinity towards were canagliflozin, empagliflozin, lumacaftor, eprosartan, dapagliflozin. The top-scoring showed stable protein-ligand complexation (PLC)with revealed RMSD / RMSF analysis. silico ADMET prediction analysis assessed pharmacokinetic profiles these wherein they favourable drug-likeness properties. These promising results indicate scope developing validating agonists disease models.

Language: Английский

In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation – Targeting Mpro and pan-coronavirus post-fusion Spike protein DOI Creative Commons

Sumit Kumar Mandal,

MD Muzaffar-Ur Rehman,

Ashish Katyal

et al.

Journal of Traditional and Complementary Medicine, Journal Year: 2023, Volume and Issue: 14(1), P. 55 - 69

Published: July 13, 2023

Novel nature of the viral pathogen SARS-CoV-2 and absence standard drugs for treatment, have been a major challenge to combat this deadly infection. Natural products offer safe effective remedy, which traditional ethnic medicine can provide leads. An indigenous poly-herbal formulation, Kabasura Kudineer from Siddha system was evaluated here using combination computational approaches, identify potential inhibitors against two anti-SARS-CoV-2 targets - post-fusion Spike protein (structural protein) main protease (Mpro, non-structural protein). We docked 32 phytochemicals formulation glycoprotein Mpro followed by molecular dynamics Schrodinger software. Drug-likeness analysis performed machine learning (ML) approach pkCSM. The binding affinity in revealed following top-five bioactives: Quercetin > Luteolin Chrysoeriol 5-Hydroxy-7,8-Dimethoxyflavone Scutellarein target, Gallic acid Piperlonguminine Elemol Piperine target. exhibited stability complexation with their respective viral-targets favourable free energy change as simulations MM-PBSA analysis. In silico predicted pharmacokinetic profiling these ligands appropriate drug-likeness properties. These outcomes provide: (a) mechanism anti-viral efficacy targeting (b) top bioactive lead-molecules that may be developed natural product-based pharmacotherapy pleiotropic protective effects leveraged manage co-morbidities associated COVID-19.

Language: Английский

Citations

6
Molecular bioprospection of Helianthus annuus L. (sunflower) cypselae for antidiabetic therapeutics through network pharmacology, density functional theory and molecular dynamics simulation DOI

Athika Rampadarath,

‪Jamiu Olaseni Aribisala, Nokwanda P. Makunga

et al.

South African Journal of Botany, Journal Year: 2023, Volume and Issue: 162, P. 72 - 95

Published: Sept. 8, 2023

Language: Английский

Citations

6
Waste to Medicine: Evidence from Computational Studies on the Modulatory Role of Corn Silk on the Therapeutic Targets Implicated in Type 2 Diabetes Mellitus DOI Creative Commons

Ayesha Akoonjee,

Adedayo Ayodeji Lanrewaju, Fatai Oladunni Balogun

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(12), P. 1509 - 1509

Published: Dec. 11, 2023

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and/or defective production in the human body. Although antidiabetic action of corn silk (CS) well-established, understanding mechanism (MoA) behind this potential lacking. Hence, study aimed to elucidate MoA different samples (raw and three extracts: aqueous, hydro-ethanolic, ethanolic) as a therapeutic agent for management T2DM using metabolomic profiling computational techniques. Ultra-performance liquid chromatography-mass spectrometry (UP-LCMS), silico techniques, density functional theory were used compound identification predict MoA. A total 110 out 128 identified secondary metabolites passed Lipinski’s rule five. The Kyoto Encyclopaedia Genes Genomes pathway enrichment analysis revealed cAMP hub signaling pathway, which ADORA1, HCAR2, GABBR1 key target genes implicated pathway. Since gallicynoic acid (−48.74 kcal/mol), dodecanedioc (−34.53 tetradecanedioc (−36.80 kcal/mol) interacted well with GABBR1, respectively, are thermodynamically stable their formed compatible complexes, according post-molecular dynamics simulation results, they suggested drug candidates therapy via maintenance normal glucose homeostasis pancreatic β-cell function.

Language: Английский

Citations

6
Do anti-obesity medical treatments have a direct effect on adipose tissue? DOI Creative Commons
Bruno Vergès

Annales d Endocrinologie, Journal Year: 2024, Volume and Issue: 85(3), P. 179 - 183

Published: June 1, 2024

During the past years, several drugs have been developed for treatment of obesity. Some are already used in clinical practice: orlistat, GLP-1 receptor agonists (RA), GLP-1/GIP biagonists and melanocortin 4 (MC4R) agonist, setmelanotide. should be available future: GLP-1/glucagon biagonists, GLP-1/GIP/glucagon triagonists. These act mainly by reducing food intake or fat absorption. However, many them show specific effects on adipose tissue. All these significant reduction mass and, more particularly visceral fat. If most drugs, except shown to increase energy expenditure rodents with enhanced thermogenesis, this has not yet clearly demonstrated humans. triagonist stimulating glucagon seem a potent effect thermogenesis tissue thus, expenditure. Most production adiponectin reduce pro-inflammatory cytokines GLP-1RAs size adipocytes promote their differentiation. GLP-1RAS reduce, tissue, expression genes involved lipogenesis. Further studies still needed clarify precise roles, dedicated

Language: Английский

Citations

2
Exploring the therapeutic mechanisms of millet in obesity through molecular docking, pharmacokinetics, and dynamic simulation DOI Creative Commons
Komal G. Lakhani, Roslida Abd Hamid,

Sheetal Gupta

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 18, 2024

Obesity, a prevalent global health concern, is characterized by excessive fat accumulation, which confers significant nutritional and risks, including shortened lifespan diminished wellbeing. Central to the regulation of energy balance food intake mass obesity-associated (FTO) protein, modulates interplay between caloric consumption expenditure. Given its pivotal role in obesity regulation, identification effective inhibitors targeting FTO protein imperative for developing therapeutic interventions. Currently available anti-obesity drugs are often plagued undesirable side effects. In contrast, natural plant-derived bioactive compounds gaining prominence pharmaceutical industry due their efficacy lower incidence adverse Little Millet, traditional cereal known rich profile high satiety index, was investigated this study using molecular docking dynamics simulation approach potential as an agent. Our research demonstrates that four from Millet exhibit superior binding energies ranging 7.22 8.83 kcal/mol, compared standard drug, orlistat, has 5.96 kcal/mol. These fulfilled all drug-like criteria, Lipinski, Ghose, Veber, Egan, Muegge rules, exhibited favorable profiles terms distribution, metabolism, prolonged half-life without toxicity. Conversely, orlistat associated with hepatotoxicity, reduced half-life, multiple violations drug-likeness parameters, undermining efficacy. Molecular simulations Gibbs free assessments revealed identified maintain stable interactions key residues protein’s active site. We propose further validation through extensive vitro , vivo clinical studies ascertain these combating obesity.

Language: Английский

Citations

2
Antihyperlipidemic mechanisms of a formula containing Curcuma xanthorrhiza, Sechium edule, and Syzigium polyanthum: In silico and in vitro studies DOI
Frangky Sangande, Kurnia Agustini, Krisyanti Budipramana

et al.

Computational Biology and Chemistry, Journal Year: 2023, Volume and Issue: 105, P. 107907 - 107907

Published: June 20, 2023

Language: Английский

Citations

4
Preferential inhibition of α-amylase by cinnamaldehyde-based hydrazones: A comparative study DOI

Chanchal Vashisth,

Neera Raghav

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: unknown, P. 136654 - 136654

Published: Oct. 1, 2024

Language: Английский

Citations

1
Key Role of PPAR-γ-Mediated Suppression of the NFκB Signaling Pathway in Rutin's Antidepressant Effect DOI

Shu-Yuan Yin,

Xinxin Shao,

Shi-Yu Shen

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: unknown, P. 156178 - 156178

Published: Oct. 1, 2024

Language: Английский

Citations

1
Antihyperglycemic and Hypolipidemic Activities of Flavonoids Isolated from Smilax Dominguensis Mediated by Peroxisome Proliferator-Activated Receptors DOI Creative Commons
Erandi Ortiz-Barragán, Samuel Estrada‐Soto, Abraham Giacoman‐Martínez

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(11), P. 1451 - 1451

Published: Oct. 30, 2024

: Mexican people use Smilax dominguensis as a traditional medicine for diabetes control. Some reports have shown an anti-hyperglycemic effect in animal models. In the current research, chemical bio-guided fractionation vitro and silico was performed to identify compounds with hypolipidemic effects through PPARγ/α dual agonist activity because they regulate genes involved energy storage burning, such GLUT4 FATP.

Language: Английский

Citations

1
Hydroethanolic Extract of Morus nigra L. Leaves: A Dual PPAR-α/γ Agonist with Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated RAW 264.7 DOI Creative Commons
Amanda de Assis Carneiro, Simone Batista Pires Sinoti, Marcela Medeiros de Freitas

et al.

Plants, Journal Year: 2022, Volume and Issue: 11(22), P. 3147 - 3147

Published: Nov. 17, 2022

Inhibition of systemic inflammation has been a beneficial strategy in treating several non-communicable diseases, which represent one the major causes mortality world. The Peroxisome Proliferator-Activated Receptors (PPAR) are interesting pharmacological targets, since they can act both through metabolic and anti-inflammatory pathways. Morus nigra L. flavonoids its chemical composition with recognized anti-oxidant activity often associated activity. Therefore, this study aimed to evaluate hydroethanolic extract M. leaves’ ability activate PPAR promote effects lipopolysaccharide (LPS)-stimulated murine macrophage cells. leaf was prepared by cold maceration, profile obtained HPLC-DAD. Activation α γ evaluated luciferase reporter assay. assessed measuring reactive oxygen species (ROS), nitric oxide (NO), Tumor Necrosis Factor-α (TNF-α) RAW 264.7 cells after stimulation LPS from Escherichia coli. HPLC-DAD analysis identified two compounds: rutin isoquercitrin. showed agonist for types PPAR, γ, although compounds, isoquercitrin, did not significantly receptors. In addition, reduced production ROS, NO, TNF-α. Treatment specific PPAR-α antagonist, GW 6471, able partially block effect caused extract.

Language: Английский

Citations

6