Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1422 - 1422

Published: Jan. 11, 2023

Excess body weight is frequently associated with low-grade inflammation. Evidence indicates a relationship between obesity and cancer, as well other diseases, such diabetes non-alcoholic fatty liver disease, in which inflammation the actions of various adipokines play role pathological mechanisms involved these disorders. Leptin mainly produced by adipose tissue proportion to fat stores, but it also synthesized organs, where leptin receptors are expressed. This hormone performs numerous brain, related control energy homeostasis. It neurogenesis neuroprotection, central resistance some neurological disorders, e.g., Parkinson’s Alzheimer’s diseases. In peripheral tissues, implicated regulation metabolism, bone density muscle mass. All can be affected changes levels this hormone. review will present recent advances molecular action their underlying roles situations, may interest for revealing new approaches treatment diseases adipokine might compromised.

Language: Английский

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Fecal fermentation and high-fat diet-induced obesity mouse model confirmed exopolysaccharide from Weissella cibaria PFY06 can ameliorate obesity by regulating the gut microbiota

Carbohydrate Polymers, Journal Year: 2023, Volume and Issue: 318, P. 121122 - 121122

Published: June 15, 2023

Language: Английский

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Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 390 - 390

Published: Feb. 24, 2024

Aging populations worldwide are placing age-related diseases at the forefront of research agenda. The therapeutic potential natural substances, especially propolis and its components, has led to these products being promising agents for alleviating several cellular molecular-level changes associated with diseases. With this in mind, scientists have introduced a contextual framework guide future aging research, called hallmarks aging. This encompasses various mechanisms including genomic instability, epigenetic changes, mitochondrial dysfunction, inflammation, impaired nutrient sensing, altered intercellular communication. Propolis, rich array bioactive compounds, functions as potent functional food, modulating metabolism, gut microbiota, immune response, offering significant health benefits. Studies emphasize propolis' properties, such antitumor, cardioprotective, neuroprotective effects, well ability mitigate oxidative stress, DNA damage, pathogenic bacteria growth. article underscores current scientific evidence supporting role controlling molecular characteristics linked hallmarks, hypothesizing geroscience research. aim is discover novel strategies improve quality life older individuals, addressing existing deficits perspectives area.

Language: Английский

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Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

ChemistrySelect, Journal Year: 2022, Volume and Issue: 7(46)

Published: Dec. 12, 2022

Abstract One of the most prevalent chronic metabolic disorders, diabetes mellitus, is defined by hyperglycemia and emergence microvascular macrovascular pathology unique to diabetes. Several problems are primarily caused persistent hyperglycemia. In this study, aldose reductase (AR) sorbitol dehydrogenase (SDH) enzymes were purified using chromatographic techniques from sheep kidneys α‐glycosidase purchased commercially. The inhibitory effect seven acylthiourea compounds on activity these associated with was investigated. As a result studies, acyl thioureas showed an inhibition at micromolar level studied enzymes. active compound dimethyl 1‐((4‐methoxybenzoyl)carbamothioyl)‐5,5‐diphenylpyrrolidine‐2,4‐dicarboxylate ( 2 c ) had excellent selectivity AR K i : 0.200±0.024 μM 1‐((2,4‐dichlorobenzoyl)carbamothioyl)‐5,5‐diphenylpyrrolidine‐2,4‐dicarboxylate g SDH 0.114±0.01 055±0.01 μM, respectively. findings suggest that our study will contribute development innovative and/or alternative treatment strategies in future since have effective capacity critical

Language: Английский

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An update on current type 2 diabetes mellitus (T2DM) druggable targets and drugs targeting them

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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Exploring the anti-diabetic potential of barnyard millet: insights from virtual screening, MD simulation and MM-PBSA

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: March 14, 2025

Barnyard millet (Echinochloa frumentacea) is a nutritionally superior grain and rich source of dietary fiber, protein. It helps in managing health issues such as malnutrition, diabetes, obesity, celiac disease. Its low content slowly digestible carbohydrates promotes gradual release glucose, helping to maintain stable blood glucose levels. The present study aims identify screen phytochemicals the barnyard explore its anti-diabetic activity through an in-silico study. Gas chromatography-mass spectrometry (GC-MS) analyses seed extract revealed occurrence 73 bioactive compounds that are known possess variety pharmacological activities. Based on virtual screening analysis, interacted with five different diabetic targets, diosgenin demonstrating lowest binding affinity across four receptors. Specifically, showed -9.2 kcal/mol Insulin receptor (PDB ID: 1IR3), -8.7 Peroxisome proliferator-activated receptors 3G9E), -7.5 Tyrosine phosphatase 1-beta (2F70), -6.5 Glucagon 5EE7). For Aldose reductase 4XZH), Docosahexaenoic acid exhibited -9.9 kcal/mol. dynamic behavior 2F70-Diosgenin docked complexes throughout 500 ns trajectory run was investigated further. RMSD RMSF reveal complex remains structurally stable. free energies were computed using Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) methodology. calculation results show predicted These suggest stable, highlighting potential for further wet lab validation.

Language: Английский

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Profiling of Antidiabetic Bioactive Flavonoid Compounds from an Edible Plant Kudzu (Pueraria lobata)

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(28), P. 15704 - 15714

Published: July 8, 2024

(Willd.) Ohwi, known as kudzu and used a "longevity powder" in China, is an edible plant which rich flavonoids believed to be useful for regulating blood sugar treating diabetes, although the modes of action are unknown. Here, total 53 including 6 novel compounds were isolated from using multidimensional preparative liquid chromatography. The flavonoid components found lower levels, promote urine levels mice, reduce volume. Molecular docking vitro assays suggested that antidiabetic effect was attributed at least three targets: sodium-dependent glucose transporter 2 (SGLT2), protein tyrosine phosphatase-1B (PTP1B), alpha-glucosidase (AG). This study suggests possible mechanism may involve synergistic multiple active kudzu.

Language: Английский

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Development, biological evaluation, and molecular modelling of some benzene-sulfonamide derivatives as protein tyrosine phosphatase-1B inhibitors for managing diabetes mellitus and associated metabolic disorders

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Exploring new inhibitors with good bioavailability and high selectivity for managing type 2 diabetes mellitus (T2DM) its associated complications is a major challenge research, academia, the pharmaceutical industry. Protein tyrosine phosphatase-1B (PTP1B) arose as an important negative regulator in insulin signaling pathways metabolic disorders, including T2DM obesity. Novel neutral compounds benzene-sulfonamide scaffold were designed synthesized based on structural- ligand-based drug design strategies fragment growth. Promising hits against PTP1B identified through

Language: Английский

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Promising Directions for Regulating Signaling Pathways Involved in the Type 2 Diabetes Mellitus Development (A Review)

Russian Journal of Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 50(4), P. 1263 - 1284

Published: Aug. 1, 2024

Language: Английский

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An in silico analysis of the interaction of marine sponge-derived bioactive compounds with type 2 diabetes mellitus targets DPP-4 and PTP1B

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: Jan. 8, 2024

Type 2 diabetes is a medical condition involving elevated blood glucose levels resulting from impaired or improper insulin utilization. As the number of type cases increases each year, there an urgent need to develop novel drugs having new targets and/or complementing existing therapeutic protocols. In this regard, marine sponge-derived compounds hold great potential due their potent biological activity and structural diversity. study, small library 50 were examined for towards targets, namely dipeptidyl peptidase-4 (DPP-4) protein tyrosine phosphatase 1B (PTP1B). The first subjected molecular docking on models based respective co-crystal structures assess binding free energies (BFE) conformations. Clustering analysis yielded BFE that ranged 24.54 kcal/mol −9.97 DPP-4, −4.98 −8.67 PTP1B. Interaction top ten with most negative target showed similar intermolecular interactions key interacting residues as in previously solved structure. These absorption, distribution, metabolism, excretion, toxicity (ADMET) profiling characterize drug-likeness combining results these analyses, (S)-6'-debromohamacanthin B was identified multi-target inhibitor DPP-4 PTP1B, favorable interaction, no Lipinski violations, good gastrointestinal (GI) tract blood-brain barrier (BBB) penetration, predicted toxicity. Finally, interaction two proteins validated using dynamics simulations over 100 ns through RMSD, radius gyration, PCA, mechanics Poisson-Boltzmann surface area (MMPBSA) confirming proteins.

Language: Английский

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