Cited by Identification of PPAR β/δ agonists using a drug-repurposing approach by computational HTVS and molecular docking/ dynamics simulation

A Comprehensive Review of Phytonutrients as a Dietary Therapy for Obesity DOI

Shahida Anusha Siddiqui, Iskandar Azmy Harahap,

Priyanka Suthar

et al.

Foods, Journal Year: 2023, Volume and Issue: 12(19), P. 3610 - 3610

Published: Sept. 28, 2023

Obesity is a complex medical condition mainly caused by eating habits, genetics, lifestyle, and medicine. The present study deals with traditional diets like the Mediterranean diet, Nordic African Heritage Asian DASH, as these are considered to be sustainable for curing obesity. However, bioavailability of phytonutrients consumed in diet may vary, depending on several factors such digestion absorption phytonutrients, interaction other substances, cooking processes, individual differences. Hence, phytochemicals, polyphenols, alkaloids, saponins, terpenoids, etc., have been investigated assess their efficiencies safety prevention treatment These phytochemicals anti-obesity effects, mediated via modulation many pathways, decreased lipogenesis, lipid absorption, accelerated lipolysis, energy intake, expenditure, preadipocyte differentiation proliferation. Owing new food formulations incorporating were introduced that can beneficial reducing prevalence obesity promoting public health.

Language: Английский

Citations

Identification and exploration of quinazoline-1,2,3-triazole inhibitors targeting EGFR in lung cancer DOI

Sunil Kumar, Sounok Sengupta, Iqra Ali

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 41(21), P. 11353 - 11372

Published: April 28, 2023

Epidermal growth factor receptor (EGFR) enhances lung cancer development, due to their inability permeate the cell membrane, secreted factors work through specialized signal transduction pathways. The purpose of this study is find out a novel anticancer agent that inhibits EGFR and reduces chances cancer. A series triazole-substituted quinazoline hybrid compounds were designed by Chemdraw software docked against five different crystallographic tyrosine kinase domain (TKD). For docking visualization PyRx, Autodock vina, Discovery studio visualizer used. Molecule-14, Molecule-16, Molecule-19, Molecule-20, Molecule-38 showed significant affinity but Molecule-19 excellent binding (-12.4 kcal/mol) with kinase. superimposition co-crystalized ligand hit compound shows similar conformation at active site (PDB ID: 4HJO) indicating coupling pharmaceutically active. good bioavailability score (0.55) no sign carcinogenesis, mutagenesis, or reproductive toxicity properties. MD simulation MMGBSA represent stability free energy demonstrating (Molecule-19) may be used as lead compound. also ADME properties, scores, synthetic accessibility fewer signs toxicity. It was observed potential inhibitor side effects than reference molecule. Additionally, molecular dynamics revealed stable nature protein-ligand interaction provided information about amino acid residues involved in binding. Overall, led identification inhibitors favorable pharmacokinetic We believe outcome can help develop more potent drug-like molecules tackle human

Language: Английский

Citations

The Adipocyte–Macrophage Relationship in Cancer: A Potential Target for Antioxidant Therapy DOI

Sofía Sanhueza, Layla Simón, Mariana Cifuentes

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(1), P. 126 - 126

Published: Jan. 4, 2023

Obesity has emerged as a major public health concern with staggering 39% worldwide prevalence of 2021. Given the magnitude problem and considering its association chronic low-grade systemic inflammation, it does not come surprise that obesity is now considered one risk factors for development several diseases, such diabetes, cardiovascular problems, cancer. Adipose tissue dysfunction in taken center stage understanding how changes components, particularly adipocytes macrophages, participate processes. In this review, we will initially focus on adipose upon excess fat accumulation generate endocrine signals promote cancer development. Moreover, tumor microenvironment or stroma, which also critical development, contains macrophages adipocytes, which, reciprocal paracrine communication cells, relevant signals. We discuss signaling between favors progression. Finally, reactive oxygen species many these pathways, summarize information available antioxidants can limit effects due to dysfunctional components obesity.

Language: Английский

Citations

Natural compounds as obesity pharmacotherapies DOI

Xinyuan Zhao,

Ji‐Qiu Wang,

G. Gregory Neely

et al.

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 38(2), P. 797 - 838

Published: Dec. 11, 2023

Abstract Obesity has become a serious global public health problem, affecting over 988 million people worldwide. Nevertheless, current pharmacotherapies have proven inadequate. Natural compounds garnered significant attention due to their potential antiobesity effects. Over the past three decades, ca. 50 natural been evaluated for preventive and/or therapeutic effects on obesity in animals and humans. However, variations efficacies among these substantial, owing differences experimental designs, including animal models, dosages, treatment durations, administration methods. The feasibility of employing as remained uncertain. In this review, we systematically summarized efficacy mechanisms action each compound models. This comprehensive review furnishes valuable insights development medications based compounds.

Language: Английский

Citations

Investigating the antioxidant activity enhancer effect of Cyamopsis tetragonoloba seed extract on phenolic phytochemicals DOI

Tripti Joshi,

Sumit Kumar Mandal,

Sonakshi Puri

et al.

Frontiers in Plant Science, Journal Year: 2023, Volume and Issue: 14

Published: March 8, 2023

Phenolic phytochemicals are known for antioxidant-mediated pharmacological effects in various diseases (diabetes, cancer, CVDs, obesity, inflammatory and neurodegenerative disorders). However, individual compounds may not exert the same biological potency as combination with other phytochemicals. Cyamopsis tetragonoloba (Guar), an underutilized semi-arid legume which has been used a traditional food Rajasthan (India), is also source of important industrial product guar gum. studies on its activity, like antioxidant, limited.We tested effect C. seed extract to enhance antioxidant activity well-known dietary flavonoids (quercetin, kaempferol, luteolin, myricetin, catechin) non-flavonoid phenolics (caffeic acid, ellagic taxifolin, epigallocatechin gallate (EGCG), chlorogenic acid) using DPPH radical scavenging assay. The most synergistic was further validated cytoprotective anti-lipid peroxidative vitro cell culture system, at different concentrations extract. LC-MS analysis purified performed.In cases, we observed synergy lower (0.5-1 mg/ml). concentration 0.5 mg/ml enhanced Epigallocatechin (20 µg/ml) by 2.07-folds, implicating potential act enhancer. This extract-EGCG diminished oxidative stress nearly double-fold when compared phytochemical treatments culture. revealed some previously unreported metabolites, including catechin hydrate, myricetin-3-galactoside, gossypetin-8-glucoside, puerarin (daidzein-8-C-glucoside) possibly explains enhancer effect. outcomes this study could be development effective nutraceutical/dietary supplements.

Language: Английский

Citations

Unraveling PPARβ/δ nuclear receptor agonists via a drug-repurposing approach: HTVS-based ligand identification, molecular dynamics, pharmacokinetics, and in vitro anti-steatotic validation DOI

Sumit Kumar Mandal,

Mohammed Muzaffar-Ur-Rehman,

Sonakshi Puri

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(14), P. 10622 - 10633

Published: Jan. 1, 2025

Canagliflozin, empagliflozin, lumacaftor, eprosartan, and dapagliflozin were identified as hit compounds against PPARβ/δ. Canagliflozin reduced lipid accumulation oxidative stress in steatotic HepG2 cells, indicating potential anti-NAFLD effects.

Language: Английский

Citations

Quercetin promotes the uptake and antioxidant efficacy of dietary astaxanthin by activating transporter CD36 expression via the PPARγ/AMPK pathway DOI

Xiaojuan Liu,

Junlin Zhang,

Tiantian Wang

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106775 - 106775

Published: May 1, 2025

Language: Английский

Citations

Computational Approaches for PPARγ Inhibitor Development: Recent Advances and Perspectives DOI

Ayanda M. Magwenyane, Hezekiel M. Kumalo

ChemistryOpen, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

The development of peroxisome proliferator‐activated receptor gamma (PPARγ) inhibitors has attracted significant interest for treating metabolic disorders, cancer, and inflammatory diseases. This review highlights the crucial role computational modelling in advancing PPARγ inhibitor development, emphasizing how these techniques streamline identification, optimization, evaluation new drug candidates. Key methods include molecular docking, QSAR, dynamics simulations, which enhance efficiency accuracy design. Computational deepened our understanding binding mechanisms conformational dynamics, allowing researchers to predict optimize ligand‐receptor complex stability. Despite advancements, challenges remain, such as improving predictions pharmacokinetic properties (ADME) evaluate drug‐like qualities. In conclusion, significantly enhanced discovery offering opportunities address Continued refinement models, combined with experimental validation emerging technologies, is overcoming current limitations achieving successful clinical outcomes.

Language: Английский

Citations

Discovery of a novel binding pocket in PPARγ for partial agonists: structure-based virtual screening identifies ginsenoside Rg5 as a partial agonist promoting beige adipogenesis DOI

Zhen Wang,

Kexin Shui,

Zehui Zhang

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: May 8, 2025

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key target for metabolic disorders that contribute to obesity and type 2 diabetes mellitus (T2DM). However, full agonists such as thiazolidinediones (TZDs) have limitations in terms of side effects. Selective PPARγ modulators (SPPARγMs) alternative binding pockets offer the potential safer partial agonists. Here, we employed six computational algorithms (Fpocket, DeepSite, CavityPlus, DoGSiteScorer, CASTpFold, POCASA) identify novel allosteric pocket (pocket 6-5) ligand-binding domain (LBD), localized at helix 3 (H3), (H2), 2'(H2'), β-sheet interface. A virtual screening 4,097 natural compounds from traditional Chinese medicine (TCM) libraries was conducted, which led identification ginsenoside Rg5 (TWSZ-5) top hit. Molecular docking molecular dynamics (MD) revealed TWSZ-5 stabilizes 6-5 through hydrogen bonds with Ser342, Gln345, Lys261, Lys263. promoted beige adipocyte differentiation adipose-derived stem cells (ADSCs) vitro, upregulating Ucp1, Prdm16, Cpt1α, Pgc1α. The present study identifies SPPARγM utilizes an enhance thermogenesis while mitigating adverse These findings emphasize TCM derivatives structure-based strategies develop antidiabetic therapies precision pharmacology.

Language: Английский

Citations

Targeting lipid-sensing nuclear receptors PPAR (α, γ, β/δ): HTVS and molecular docking/dynamics analysis of pharmacological ligands as potential pan-PPAR agonists DOI

Sumit Kumar Mandal,

Sonakshi Puri,

Banoth Karan Kumar

et al.

Molecular Diversity, Journal Year: 2023, Volume and Issue: 28(3), P. 1423 - 1438

Published: June 6, 2023

Language: Английский

Citations